Page last updated: 2024-10-24

phagocytosis, engulfment

Definition

Target type: biologicalprocess

The internalization of bacteria, immune complexes and other particulate matter or of an apoptotic cell by phagocytosis, including the membrane and cytoskeletal processes required, which involves one of three mechanisms: zippering of pseudopods around a target via repeated receptor-ligand interactions, sinking of the target directly into plasma membrane of the phagocytosing cell, or induced uptake via an enhanced membrane ruffling of the phagocytosing cell similar to macropinocytosis. [GOC:curators, ISBN:0781735149]

Phagocytosis is a fundamental process in cellular defense and tissue homeostasis, involving the engulfment and internalization of particulate matter, such as bacteria, apoptotic cells, and cellular debris. This intricate process is orchestrated by a complex interplay of cellular signaling, cytoskeletal rearrangements, and membrane dynamics.

Initiation of phagocytosis is triggered by the recognition of specific ligands on the surface of the target particle by receptors on the phagocytic cell. These receptors, such as Fc receptors, complement receptors, and scavenger receptors, bind to various targets, including antibodies, complement proteins, and pathogen-associated molecular patterns (PAMPs). Ligand binding triggers a cascade of intracellular signaling events, leading to the activation of small GTPases, such as Rac and Cdc42, which play crucial roles in cytoskeletal reorganization and membrane dynamics.

Upon receptor engagement, the phagocytic cell extends pseudopods, finger-like projections of the plasma membrane, towards the target particle. These pseudopods, driven by actin polymerization, surround the target, forming a phagocytic cup. The actin filaments, anchored to the plasma membrane by proteins like Arp2/3 complex and WASP, provide the force required for engulfment. As the phagocytic cup closes around the target, the plasma membrane fuses, creating a phagosome – a membrane-bound vesicle containing the engulfed particle.

Once the phagosome is formed, it undergoes a maturation process involving fusion with lysosomes, acidic organelles containing hydrolytic enzymes. The lysosomal enzymes degrade the ingested material, breaking it down into smaller molecules that can be recycled or excreted by the cell. This process, known as phagolysosome formation, effectively eliminates pathogens and cellular debris, preventing their harmful effects.

Phagocytosis is essential for maintaining tissue integrity, clearing apoptotic cells, and mounting an immune response against invading pathogens. Dysregulation of phagocytosis can contribute to various diseases, including autoimmune disorders, infections, and cancer. The intricate choreography of this cellular process underscores the importance of understanding its molecular mechanisms and potential for therapeutic intervention.'
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Proteins (4)

ProteinDefinitionTaxonomy
Cell division control protein 42 homologA cell division control protein 42 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P60953]Homo sapiens (human)
Myosin-9A myosin-9 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P35579]Homo sapiens (human)
High affinity immunoglobulin gamma Fc receptor IA high affinity immunoglobulin gamma Fc receptor I that is encoded in the genome of human. [PRO:CNA, UniProtKB:P12314]Homo sapiens (human)
Integrin beta-2An integrin beta-2 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P05107]Homo sapiens (human)

Compounds (21)

CompoundDefinitionClassesRoles
indoleindole;
polycyclic heteroarene
Escherichia coli metabolite
fasudilfasudil : An isoquinoline substituted by a (1,4-diazepan-1-yl)sulfonyl group at position 5. It is a Rho-kinase inhibitor and its hydrochloride hydrate form is approved for the treatment of cerebral vasospasm and cerebral ischemia.

fasudil: intracellular calcium antagonist; structure in first source
isoquinolines;
N-sulfonyldiazepane
antihypertensive agent;
calcium channel blocker;
EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor;
geroprotector;
neuroprotective agent;
nootropic agent;
vasodilator agent
ketorolac5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid : A member of the class of pyrrolizines that is 2,3-dihydro-1H-pyrrolizine which is substituted at positions 1 and 5 by carboxy and benzoyl groups, respectively.

ketorolac : A racemate comprising equimolar amounts of (R)-(+)- and (S)-(-)-5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid. While only the (S)-(-) enantiomer is a COX1 and COX2 inhibitor, the (R)-(+) enantiomer exhibits potent analgesic activity. A non-steroidal anti-inflammatory drug, ketorolac is mainly used (generally as the tromethamine salt) for its potent analgesic properties in the short-term management of post-operative pain, and in eye drops to relieve the ocular itching associated with seasonal allergic conjunctivitis. It was withdrawn from the market in many countries in 1993 following association with haemorrhage and renal failure.

Ketorolac: A pyrrolizine carboxylic acid derivative structurally related to INDOMETHACIN. It is an NSAID and is used principally for its analgesic activity. (From Martindale The Extra Pharmacopoeia, 31st ed)
amino acid;
aromatic ketone;
monocarboxylic acid;
pyrrolizines;
racemate
analgesic;
cyclooxygenase 1 inhibitor;
cyclooxygenase 2 inhibitor;
non-steroidal anti-inflammatory drug
1,4-benzodioxan1,4-benzodioxan: structure in first source
1-methylindole1-methylindole: SKATOLE refers to 3-methylindole; RN given refers to parent cpd; structure

methylindole : Any member of the class of indoles carrying one or more methyl substituents.
lovastatinlovastatin : A fatty acid ester that is mevastatin carrying an additional methyl group on the carbobicyclic skeleton. It is used in as an anticholesteremic drug and has been found in fungal species such as Aspergillus terreus and Pleurotus ostreatus (oyster mushroom).

Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver.
delta-lactone;
fatty acid ester;
hexahydronaphthalenes;
polyketide;
statin (naturally occurring)
anticholesteremic drug;
antineoplastic agent;
Aspergillus metabolite;
prodrug
chlorfenethazinechlorfenethazine: RN given refers to parent cpd; synonym elroquil refers to HCl; structurephenothiazines
sanguinarine chloride
chelerythrine chloride
2-bromohippuric acid
2-[[benzamido(sulfanylidene)methyl]amino]-5,5-dimethyl-4,7-dihydrothieno[2,3-c]pyran-3-carboxylic acidCID1067700: a pan-GTPase inhibitor; structure in first sourcethienopyran
benzotriptbenzotript: anti-gastrinic; active group is amide; structure
blisterblebbistatin : A pyrroloquinoline that is 1,2,3,3a-tetrahydro-H-pyrrolo[2,3-b]quinolin-4-one substituted by a hydroxy group at position 3a, a methyl group at position 6 and a phenyl group at position 1. It acts as an inhibitor of ATPase activity of non-muscle myosin II.

blebbistatin: structure in first source
cyclic ketone;
pyrroloquinoline;
tertiary alcohol;
tertiary alpha-hydroxy ketone
inhibitor
birt 377
a 286982A 286982: inhibits the interaction between leukocyte function-associated antigen-1 and intracellular adhesion molecule-1; structure in first source
y 27632, dihydrochloride, (4(r)-trans)-isomer
bio 1211BIO 1211: integrin alpha4beta1 inhibitor; structure in first source
secramine asecramine A: inhibits VSVG transport from the Golgi to the plasma membrane; also inhibits Cdc42-dependent cell functions; structure in first source
sar 1118lifitegrast : An N-acyl-L-alpha-amino acid obtained by formal condensation of the carboxy group of N-[2-(1-benzofuran-6-carbonyl)]-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acid with the amino group of 3-(methanesulfonyl)-L-phenylalanine. Used for treatment of keratoconjunctivitis sicca (dry eye syndrome).

lifitegrast: An LFA-1 (LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1) antagonist that is used in the treatment of DRY EYE SYNDROMES.
1-benzofurans;
isoquinolines;
L-phenylalanine derivative;
N-acyl-L-alpha-amino acid;
sulfone
anti-inflammatory drug;
lymphocyte function-associated antigen-1 antagonist
bms 777607N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide: a Met kinase inhibitor; structure in first sourcearomatic amide
nms p937NMS P937: a polo-like kinase 1 inhibitor; structure in first source