Procedimiento fagocitosis

7/23/2019 Procedimiento fagocitosis

1/26

Procedimiento

Preparar una suspensin de C. albicans que se corresponda con el tubo N3 enla escala de McFarland.

Estndar de McFarland

Tubos de McFarland 0.5 ! " #

En microbiolo$%a los estndares de turbide& de McFarland se usan comore'erencia en suspensiones bacteriol$icas para saber que el n(mero debacterias por mililitro o ms bien en )FC se$(n una escala que *a de 0.5 a !0.Estos estndares son creados al me&clar soluciones de cloruro de bario al !+con cido sul'(rico al !+ en *ol(menes espec%,cos ! para ase$urar ladensidad correcta se puede controlar usando especto'otometros.#

-os estndares pueden ser *isualmente comparados con suspensiones debacterias en salina estril o en caldos. /i la suspensin es demasiado turbiapuede aadirse dilu"ente " si no es lo su,ciente turbia se puede a$re$ar msbacterias. -a *enta1a es que no es necesario incubar ni usar equipo especialpara estimar el n(mero de bacterias.3 -a des*enta1a de este mtodo es que nodiscrimina a las bacterias *i*as de las muertas en la solucin por lo que sepuede sobreestimar la poblacin de bacterias.

Casos espec%,cos en los que se usa es en el de antibio$ramas o pruebas desensibilidad donde es necesario para estandari&ar el mtodo " se e*iten 'alsospositi*os o ne$ati*os.

Candidiasis

Candidiasis

Candida albicans P2- 3!4# lores.1p$

Culti*o en una placa de a$ar de Candida albicans

Clasi,cacin " recursos eternos

CE6!0 738

CE64 !!#

9MM :0:8;;


2/26

?i@ipedia no es un consultorio mdico A*iso mdico

Beditar datos en ?i@idata

-a candidiasis es una in'eccin '(n$ica =micosis> de cualquiera de las especiesCandida =todas ellas le*aduras> de las cuales la Candida albicans es la ms

com(n.! # Com(nmente conocida como in'eccin por deuteromicetos lacandidiasis tambin se conoce tcnicamente como candidosis moniliasis "oidiomicosis.3 D30;

-a candidiasis inclu"e in'ecciones que *an desde las super,ciales tales comola candidiasis oral " *a$initis asta las sistmicas " potencialmente mortalesconocidas como candidemias " $eneralmente se limita a personasinmunocomprometidas como pacientes con cncer trasplante o / "tambin puede presentarse en los $enitales masculinos. En pacientesinmunocomprometidos las in'ecciones por Candida pueden a'ectar el es'a$ocon el potencial de *ol*erse sistmico " causan un padecimiento muc%simoms $ra*e una 'un$emia llamada candidemia.5 :

-a candidiasis oral es mu" com(n en los bebs. No se considera patol$ica enlos bebs a menos que dure ms de un par de semanas.8

-os nios sobre todo entre los tres " los nue*e aos de edad pueden *ersea'ectados por in'ecciones crnicas de le*adura orales obser*adas


3/26

abitualmente alrededor de la boca como mancas blancas. /in embar$o noes un padecimiento com(n.

-os s%ntomas de la candidiasis pueden *ariar se$(n el rea que ste a'ecte.

n'ecciones de la *a$ina o de la *ul*a pueden causar pica&n $ra*e ardordolor irritacin " una descar$a blanquecina o blanco $risceo con consistenciacomo de requesn a menudo con una apariencia similar a $rumos. Estoss%ntomas tambin estn presentes en la ms com(n *a$inosis bacteriana.; Enun estudio publicado el #00# en la Hournal o' 9bstetrics and I"necolo$"=Je*ista de 9bstetricia " Iinecolo$%a> slo una parte de las mu1eres que seestaban automedicando para una in'eccin por le*aduras en realidad ten%anuna in'eccin por le*aduras mientras que la ma"or%a ten%a *a$inosisbacteriana o una in'eccin de tipo mito.4 -os s%ntomas de una in'eccin en los$enitales masculinos inclu"en mancas o lla$as ro1as cerca de la cabe&a delpene o en el prepucio pica&n se*era o una sensacin de ardor. -a candidiasisdel pene tambin puede tener una descar$a blanca pero es poco com(n.

CausasBeditar

Kase tambinD Candida albicans

-as le*aduras de Candida $eneralmente estn presentes en seres umanossanos en particular sobre la piel pero su crecimiento suele *erse limitado$racias al sistema inmune a la competencia de otros microor$anismos comobacterias que ocupan los mismos lu$ares del or$anismo!0 o por la relati*aresequedad de la piel pues Candida requiere la umedad para su

crecimiento.!!

/e aisl C. albicans de la *a$ina del !4 por ciento de un $rupo de mu1eresaparentemente sanas es decir mu1eres que presentaban pocos s%ntomas oque no ten%an nin$(n s%ntoma de in'eccin. El uso eterno de deter$entes o deducas o al$unas irre$ularidades internas =ormonales o ,siol$icas> puedenpro*ocar trastornos en la Gora *a$inal abitual que inclu"e sobre todo bacilosde cido lctico como por e1emplo -actobacillus " $eneran un crecimientoecesi*o de clulas de Candida " pro*ocan s%ntomas de in'eccin comoinGamacin local.!# El embara&o " el uso de anticoncepti*os orales se

consideran 'actores de ries$o.!3 -a diabetes mellitus " el uso de antibiticosantibacteriales tambin estn relacionados con una ma"or incidencia dein'ecciones por on$os.! /e a descubierto que las dietas ricas encarboidratos simples inGu"en sobre las tasas de candidiasis oral!5 " laterapia de reempla&o ormonal " los tratamientos de la in'ertilidad tambinpueden ser 'actores predisponentes.!: El uso de tra1es de bao (medos porperiodos lar$os tambin pueden ser un 'actor de ries$o.!8


4/26

)n sistema inmune debilitado o poco desarrollado o en'ermedades metablicascomo la diabetes son 'actores de predisposicin si$ni,cati*os de lacandidiasis.!; 2a" en'ermedades o situaciones o padecimientos *inculadoscon la candidiasisD el K2L/ al !0+. ElO92 disuel*e las clulas cutneas pero de1a las clulas Candida intactas "permite la *isuali&acin de pseudoi'as " las clulas de la le*adura en ciernest%pico de mucas especies de Candida.

Para el mtodo de culti*o un bastoncillo estril se 'rota sobre la super,cie dela piel in'ectada. El bastoncillo se pasa lue$o por un medio de culti*o. El culti*o


5/26


6/26

antimicticos pero tambin se podr%a desarrollar una resistencia contra estosotros a$entes antimicticos. -as resistencias a los a$entes antimicticos "antimicrobiales en $eneral se pueden aumentar en presencia de metalespesados como el mercurio30 por lo que una candidiasis resistente a losantimicrobiales puede interpretarse como un s%ntoma compatible con unposible en*enenamiento por mercurio. -as resistencias a los antimicrobiales " alos metales pesados suelen coincidir en los mismos plsmidos lo que eplica laresistencia de las cndidas a ambos 'actores.

2istoriaBeditar

El $nero Candida " especie C. albicans 'ueron descritos por la botnicaCristine Marie 7er@out en su tesis doctoral en la )ni*ersidad de )trect en!4#3. Con los aos la clasi,cacin de los $neros " especies ane*olucionado. Nombres obsoletos de este $nero inclu"en M"cotorula "

Torulopsis. -a especie a sido tambin conocida en el pasado como Monilia

albicans " 9idium albicans. -a clasi,cacin actual es nomen conser*andum loque si$ni,ca que el nombre es autori&ado para su uso por el Con$resonternacional de 7otnica =7C>.3!

El $nero Candida inclu"e alrededor de !50 especies distintas sin embar$oslo unas pocas son conocidas por causar in'ecciones en seres umanos. C.albicans es la especie pato$nica ms si$ni,cati*a. 9tras especies Candidapato$nicas en umanos inclu"en C. tropicalis C. $labrata C. @rusei C.parapsilosis C. dubliniensis " C. lusitaniae.

/ociedad " culturaBeditar

Al$unos de'ensores de la medicina alternati*a postulan una amplia presenciade candidiasis sistmica =o s%ndrome de ipersensibilidad por cndida aler$ia ala le*adura o crecimiento ecesi*o de Candida $astrointestinal> unpadecimiento mdicamente no reconocido.3# -a opinin 'ue ampliamentepromo*ida en un libro publicado por el doctor ?illiam Croo@33 que planteabacomo iptesis que una *ariedad de s%ntomas comunes tales como la 'ati$a els%ndrome premenstrual =/PM> la dis'uncin seual el asma la psoriasisproblemas di$esti*os " urinarios la esclerosis m(ltiple " los dolores musculares

podr%an ser causados por in'ecciones subcl%nicas de Candida albicans.33 Croo@su$iere una *ariedad de remedios para tratar estos s%ntomas lo que inclu"emodi,caciones en la dieta antimicticos con receta e irri$acin del colon. Conla ecepcin de al$unos estudios dietticos en la seccin de in'eccin urinariala medicina con*encional no a usado la ma"or%a de estas alternati*as "a queno a" e*idencia cient%,ca que pruebe la e'ecti*idad de estos tratamientos oque la candidiasis sistmica subcl%nica sea un dia$nstico *iable.3 35 3: 38


7/26

En !440 el pro*eedor de medicina alternati*a Natures ?a" ,rm un acuerdode consentimiento FTC de no des*irtuar en la publicidad nin$una prueba deautodia$nstico acerca de condiciones de candidiasis o acer cualquierrepresentacin sin 'undamento acerca de la capacidad de cualquier alimento osuplemento para el control de condiciones de le*aduras con una multa deQ30.000 a nombre de los nstitutos Nacionales de /alud para in*esti$acionesen una candidiasis $enuina.3#

PJ9T9C9-9D FJ9T/ /ANI)RNE9

Concepto

-a etensin san$u%nea o 'rotis es una ,na pel%cula de san$re etendida sobreun porta de tal manera que las clulas estn dispuestas en una sola capa.

/e utili&a para la obser*acin de las clulas san$u%neas para lo cual tras laetensin de la muestra se procede a su ,1acin " tincin.

/i queremos estudiar la mor'olo$%a en clulas *i*as se pueden usar colorantes*itales. /e trata de colorantes capaces de ,1arse a los distintos componentescelulares sin destruir la clula de 'orma inmediata. /e usan mu" diluidos paradisminuir su accin tica aumentando as% el tiempo que las clulas puedenser obser*adas *i*as.

-os colorantes *itales ms conocidos son el ro1o neutro el a&ul de metileno ela&ul de cresil brillante el a&ul tripn " el *erde Hanus.

Material

S


8/26

! Co$er una pequea cantidad de san$re del tubo con una pipeta dePasteur " depositarla en un etremo del porta.

# Colocar otro portaob1etos sobre el primero con un n$ulo de unos 5despla&ndolo asta que contacte con la $ota de san$re.

3 Cabe&aD &ona inicial. -os emat%es pueden estar 'ormando ms de una capa.

b>CuerpoD los emat%es se disponen 'ormando una sola capa en una proporcinequilibrada. Es la &ona ideal para el estudio celular.

c>ColaD es la &ona ,nal. -as clulas se disponen de 'orma acordonada de1andouecos entre ellas. -a cola termina de 'orma desilacada =barbas>.


9/26

Etensiones de'ectuosas

a> etensiones en las que se a puesto una $ota mu" $rande. /e lle$a al ,naldel porta sin que la $ota a"a sido etendida no dando lu$ar a que se 'ormenlas barbas.

b> etensiones en las que el porta se le*anta antes de acabar de acer laetensin. No se 'orma la cola.

c> etensiones con &onas a$u1ereadas debido a la presencia de $rasa en losportaob1etos por 'alta de limpie&a.

d> etensiones en las que los bordes coinciden con los del porta por aberesperado que la $ota por capilaridad se etendiera por todo el borde del portaetensor.

e> etensiones con alternancia de &onas $ruesas " ,nas que le danaspecto de persiana. /e producen cuando la *elocidad dedesli&amiento no a sido omo$nea.

Tincin de ?ri$t

-a tincin de ?ri$t es un tipo de tincin usada en istolo$%a para 'acilitar ladi'erenciacin de los tipos de clulas de la san$re. /e usa principalmente parateir 'rotis de san$re " punciones medulares para ser eaminadas almicroscopio. En cito$entica se usa para teir cromosomas para 'acilitar eldia$nstico de s%ndromes " en'ermedades.

-le*a el nombre Hames 2omer ?ri$t su in*entor que la obtu*o modi,candola tincin de JomanoUs@" en !40#.


10/26

)na tincin de JomanoUs@" consiste en a&ul de metileno " sus productos deoidacin as% como eosina V o eosina 7.

-a accin combinada de estos colorantes produce el e'ecto JomanoUs@" que

da una coloracin p(rpura a los n(cleos de los leucocitos " a los $rnulosneutro'%licos " da color rosado a los eritrocitos. -os componentes de este e'ectoson el a&ul 7 " la eosina V.

-as propiedades de tincin de JomanoUs@" dependen del enlace de loscolorantes a las estructuras qu%micas " de las interacciones del a&ul 7 " laeosina V. -os a$rupamientos de cidos nucleicos las prote%nas de los n(cleoscelulares " el citoplasma inmaduro reacti*o ,1an el a&ul 7 colorante bsico. -atincin de ?ri$t cu"o colorante est compuesto de a&ul de metileno =que tiede color a&ul las partes acidas de las clulas> " eosina =que tie las partes

alcalinas> disueltos en metanol =que permite la ,1acin de las clulas>adicionando a la preparacin buer de 'os'atos =que reidrata a las clulasdespus de la eposicin con metanol>

-a eosina V colorante cido se ,1a a los a$rupamientos bsicos de lasmolculas de emo$lobina " a las prote%nas bsicas.

The process of cellular eating, or the phagocytic swallowing of one cell by another,

is an ancient manifestation of the struggle for life itself. Following the

endosymbiotic origin of eukaryotic cells, increased cellular and then multicellular

complexity was accompanied by the emergence of autophagic mechanisms for

self-digestion. Heterophagy and autophagy function not only to protect the nutritive

status of cells, but also as defensive responses against microbial pathogens

externally or the ill effects of damaged proteins and organelles within. Because of

the key roles played by phagocytosis and autophagy in a wide range of acute and

chronic human diseases, pathologists have played similarly key roles in elucidating

basic regulatory phases for both processes. tudies in diverse organ systems

!including the brain, liver, kidney, lung, and muscle" have defined key roles for

these lysosomal pathways in infection control, cell death, inflammation, cancer,

neurodegeneration, and mitochondrial homeostasis. The literature reviewed here


11/26

exemplifies the role of pathology in defining leading-edge #uestions for continued

molecular and pathophysiological investigations into all forms of cellular digestion.

$%ife is cell activity& its uni#ueness is the uni#ueness of the cell.'Rudolf Virchow(

)nvitation to a *ellular Ban#uet)n the (+th century, udolph irchows observation that diseases originate with

changes in individual cells gave rise to the principles of cellular pathology, which

remain as cornerstones of diagnostic medicine to this day. /lthough irchow

disagreed with his contemporary %ouis 0asteur concerning the germ theory, he

recogni1ed that no single authority should be considered infallible, and advocated

for active involvement of physicians in experimental pathology. )ndeed, we now

know that diseases can be caused both by invasion of microorganisms and by

inappropriate host responses to them.The ingestion of one cell by another undoubtedly arose as a feeding mechanism in

unicellular organisms. )n a twist of fate, proteobacteria and cyanobacteria engulfed

by larger archaebacteria managed to survive, giving rise to symbiotic relationships

that form the basis of eukaryotic cells.2)n our bodies, professional phagocytes

function as a first line of defense against external pathogens, adapting ancient

engulfment mechanisms from unicellular ameboid organisms. !/n example of

normal phagocytosis of bacteria is shown in Figure (." %ikewise, as cells became

more complex, self-cannibalism by autophagy evolved from a starvation response

to fulfill additional roles in cellular homeostasis. These include the defense of the

cell against mitochondrial endosymbionts gone bad or in response to disorders of

proteostasis that threaten the cell from within. 3oreover, autophagy forms another

line of defense against microbial pathogens that can subvert the

endocytic4phagocytic system to gain entry into the cell.5
http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib1http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib2http://www.sciencedirect.com/science/article/pii/S0002944013000278#fig1http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib3http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib2http://www.sciencedirect.com/science/article/pii/S0002944013000278#fig1http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib3http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib1


12/26

Figure (.

6ormal phagocytosis of bacteria, demonstrated with immunofluorescence. / wild-type, 7*-

89:expressing, peritoneal macrophage !red" !)nvitrogen *ellTracker *3/& %ifeTechnologies, *arlsbad, */" exposed to 7;F0-expressing E. coli!green" rapidly

internali1es several bacteria.

Figure options

)t is not surprising, then, to find that a wide range of human diseases are

associated with dysfunctional phagocytosis or autophagy. ;iven that both

phagocytosis and autophagy represent integral cellular responses to pathological

stimuli, experimental pathologists have played key roles in defining central themes

for investigation since the (


13/26

ussian 1oologist, first described phagocytosis in (ority of invading bacteria enter the

tissues to be engulfed by phagocytic cells within the tissue. /s foreshadowed by

the study of Buxton and Torrey, a large body of research focused on the migratory
http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib4http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib4http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib5http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib5http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib5http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib4http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib4http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib5http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib5http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib6http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib6http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib7http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib7http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib8http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib9http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib10http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib11http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib7http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib4http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib5http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib4http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib5http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib6http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib7http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib8http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib9http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib10http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib11http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib7


14/26

patterns of phagocytes in various organs after ingestion of bacteria, including

lung, (2liver, (5spleen, (5and(and digestive tract. )n the setting of acute

pneumonia, 0ermar (2and(Cstudied the migration of leukocytes from tissues into

interstitial spaces and eventually into the lymphatic system, where the cells can

reside in lymph nodes for an extended period.)n the (+2=s and (+5=s, a debate about the cellular origin of mononuclear

phagocytes emerged in the literature. cientists struggled to determine whether

phagocytic cells originated from vascular endothelium, epithelium, or blood

monocytes.(,(and(acent to infected and inflamed tissue. /lthough

0ermar was correct in noting that infection triggers increased phagocytic cell

production and phagocyte migration to the site of infection, he was incorrect in his

theory about the origin of mononuclear phagocytes. )n (+22, impson 2(proposed

that macrophages originate from monocytes that are released into the blood in

bursts, or showers, during infection. This proposal withstood the test of time. )n

(+2, 6athan *handler Foot22stated, in an article in theAJP, that what were then

called dust cells in the lung originated from blood monocytes, not from epithelial

tissue. By the mid-2=th century, it was established that mononuclear phagocytes

originate as myeloid cells in the bone marrow, and that infection triggers release of

monocytes into the bloodstream from the bone marrow.25

The exact cytokinesignals causing this release are not yet well defined. 3onocytes extravasate

through vascular endothelial cells !which may account for 0ermars conclusions"

into tissue, where they then differentiate into macrophages and dendritic cells. 2

0hagocyte /ctivation@ / Inife That *uts Both Days

)n the mid-2=th century, researchers began to focus on defining the regulatory

crosstalk between phagocytes and their environment. The complement system

was already known to promote neutrophil chemotaxis, but in (+< it was

discovered that bacteria themselves secrete substances that draw neutrophils to

the site of infection.2C)n a (+ review in theAJP, ?nanue 2examined interactions

between phagocytes and their environment during acute and chronic inflammation,

wound healing, and normal immune responses. He not only discussed several

chemotactic stimuli, but also highlighted the importance of surface receptors on the

phagocyte that are necessary for the binding, ingestion, and degradation of foreign
http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib12http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib13http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib13http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib13http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib14http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib14http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib7http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib12http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib12http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib15http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib15http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib16http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib16http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib17http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib17http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib17http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib18http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib18http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib19http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib19http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib20http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib20http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib21http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib21http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib22http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib23http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib24http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib25http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib26http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib12http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib13http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib13http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib14http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib7http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib12http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib15http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib16http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib17http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib18http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib19http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib20http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib21http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib22http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib23http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib24http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib25http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib26


15/26

particulates ! Figure 2". The following year, it was found that disorders of

recognition and ingestion of foreign matter by these phagocytic receptors can lead

to clinical pathology.2ecent studies have confirmed that an inability to properly

complete phagocytosis contributes to a variety of diseases, including

atherosclerosis and autoimmune diseases. 2or steps in phagocytosis and autophagy. The proper induction !Aand B", cargo

targeting !C", maturation !Dand E", and completion of lysosomal clearance !F" are all

important for both phagocytosis and autophagy. For phagocytosis, the recognition of danger
http://www.sciencedirect.com/science/article/pii/S0002944013000278#fig2http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib27http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib27http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib28http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib28http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib29http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib29http://www.sciencedirect.com/science/article/pii/S0002944013000278#fig2http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib27http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib28http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib29


16/26

signals from dead cells or microbial pathogens stimulates phagocyte migration. / number of

different receptors are involved in capturing and internali1ing bacterial, apoptotic, or

particulate cargoes through a process enhanced by /tg proteins and dependent on a

proper local redox environment maintained by 7*-89. 8nce the phagocytic cargo is

inside the phagosome, concentrated production of 8 or degradative en1ymes arestimulated, depending on the ingested contents. imilarly, either general or locali1ed insults

within cells serve to trigger the membrane deposition of /tg CJ/tg (2 and of %*5 !through

Beclin (:dependent or independent mechanisms", which are essential for the extension of

autophagic membranes. Dhereas nonselective se#uestration of cytoplasm is induced by

starvation, damaged and potentially harmful cargoes need to be appropriately targeted to

%*5-bound membranes. /utophagy is also induced by phagosome-derived signals to

se#uester pathogens that escape or damage the phagosome membrane. )n turn, induction

of the autophagic pathway serves to further promote phagosome:lysosomal fusion. Thus,

these two complementary systems cooperate in removing exogenous and endogenous

danger signals to limit proinflammatory, carcinogenic, and prodeath stimuli. For both

phagocytic and autophagic pathways, inefficient lysosomal fusion or digestion can

contribute to many classes of disease !red-shaded boxes". /ccumulation of undigested

lysosomal cargo is seen in aging and in chronic granulomatous disease !*;9",

neurodegenerative diseases, and many other diseases or disorders. )nefficient utili1ation of

digested products for energy production or in the regeneration of mitochondria and other

essential cellular structures may also contribute to cell death and neurodegeneration.

Figure optionsThat phagocytes are necessary for proper wound repair in the absence of infection

was also elucidated in the (+=s. 0hagocytes were found to be re#uired not only

for removal of dead tissue, but also for communication with fibroblasts, to

stimulate fibrous scarring.5=)ndeed, as ?nanue2noted, phagocytes secrete a wide

array of substances into the environment, including en1ymes !eg, lyso1yme,

plasminogen activator, collagenase, and elastase", signals for immune modulation

!eg, lymphocyte recruitment, colony-stimulating factor, and inhibitory and lytic

signals", and complement proteins. ?nanue2also made the astute observation that

some of these secretions could be harmful to host tissueJan important concept forchronic inflammatory conditions. The pathological role of phagocytes is perhaps

best illustrated in a series ofAJParticles on atherosclerosis that appeared in the

(+


17/26

)n recent decades, much of the work on phagocytosis has been at the molecular

level, with focus on specific receptors and molecules that dictate phagocyte

behavior.5,5C,5and5)dentifying the various roles of phagocytic cells in a variety of

diseases has remained an important area of active investigation, including studies

of neurodegeneration,5ury, sarcoidosis, Cglomerulonephritis, and pulmonary fibrosis.

Frustrated 0hagocytosis and )ndigestion@ ole of eactive 8xygen pecies

8nce a phagocyte has engulfed a pathogen, the immune cell must be able to kill

the bacteria !Figure 2". 8ne method by which neutrophils and macrophages kill

ingested bacteria is through the respiratory burst, which is initiated via the 6/90H

oxidase system. / (+


18/26

)mportantly, phagocytosis itself can be impaired by a failure to appropriately

regulate oxidant levels in the body, as shown in a 2=((AJPreport of a study in

mice lacking the antioxidant en1yme extracellular superoxide dismutase !7*-

89". C(The data showed that 7*-89 is locali1ed inside macrophage and

neutrophil granules. Dhereas wild-type 7*-89 expressing macrophagesundergo efficient bacterial phagocytosis ! Figure (", phagocytosis is markedly

impaired in 7*-89 knockout macrophages !not illustrated".5This suggests that

8 production by phagocytic cells can disrupt normal phagocytosis if 7*-89 is

not present to protect the phagocyte itself from its own production of 8. This

finding further illustrates the importance of regulating 8 production, even in

settings where large #uantities of 8 are physiologically produced for bactericidal

activity. The targets through which excess superoxide or downstream 8

interfere with phagocytosis are unclear, but this study highlights an important role

for 7*-89 in phagocytic cells in promoting appropriate innate immune responses

to bacterial pathogens. C(

The antioxidant regulation of 8 production is also important for maintaining

effective phagocytic function at later stages of bacterial killing, as highlighted in a

study of the intracellular pathogen Myco!acterium a!scessus. C2This study found

that antioxidants promote killing of the mycobacteria by promoting phagosome:

lysosome fusion. Thus, regulation of 8 production in phagocytic cells appears to

be essential not only in the maintenance of normal phagocytic uptake of

bacteriaC(

but also in promoting the phagosome:lysosome fusion needed forcompletion of bacterial killing. C2

The redox environment within the phagosome is important also for adaptive

immune responses. 0roteolysis within the phagosome allows macrophages to

degrade pathogen proteins in preparation for antigen presentation. 6/90H

oxidase activity during the respiratory burst was recently shown to reversibly

oxidi1e cysteine residues in some cathepsins, which the authors propose may alter

the repertoire of antigenic peptides produced.C5/dditionally, 8 release from

phagocytes has been shown to activate 6F-MB,Ca transcription factor involved in

promoting both innate and adaptive immune responses. These findings indicatethat, even during a respiratory burst generated for bacterial killing, tight regulation

by antioxidants is important for enhancing the overall efficiency of phagocytic

functions.

3acroautophagy@ ix 9ecades of 0rogress
http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib51http://www.sciencedirect.com/science/article/pii/S0002944013000278#fig1http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib3http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib3http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib51http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib52http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib51http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib52http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib53http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib54http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib51http://www.sciencedirect.com/science/article/pii/S0002944013000278#fig1http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib3http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib51http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib52http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib51http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib52http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib53http://www.sciencedirect.com/science/article/pii/S0002944013000278#bib54


19/26

"ors d#$eure@ 7arly tudies in /utophagy

The biochemical discovery of lysosomes !speciali1ed intracellular compartments

devoted to hydrolytic digestion" by *hristian de 9uve and colleagues CCcoincided

with pathological studies of cytoplasmic inclusions reported by H.D. /ltmann in

(+CC. /ltmann !as cited by Hruban et alC" speculated that certain inclusionsrepresent a stage in the cellular reaction to in>ury in which damaged portions of

cytoplasm are se#uestered for digestion or extrusion. This process of locali1ed

cellular digestion represents the defining feature of macroautophagy. 3oreover,

mechanisms underlying autophagy-related cellular exocytosis, as predicted by this

study more than C= years ago, have recently been described. CandC

Documents

Procedimiento fagocitosis