Interaction of two phagocytic host defense systems: Fcγ receptors and complement receptor 3.
Phagocytosis of foreign pathogens by cells of the immune system is a vitally important function of innate immunity. The phagocytic response is initiated when ligands on the surface of invading microorganisms come in contact with receptors on the surface of phagocytic cells such as neutrophils, monocytes/macrophages, and dendritic cells. The complement receptor CR3 (CD11b/CD18, Mac-1) mediates the phagocytosis of complement protein (C3bi)-coated particles. Fcγ receptors (FcγRs) bind IgG-opsonized particles and provide a mechanism for immune clearance and phagocytosis of IgG-coated particles. We have observed that stimulation of FcγRs modulates CR3-mediated phagocytosis and that FcγRIIA and FcγRI exert opposite (stimulatory and inhibitory) effects. We have also determined that an intact FcγR immunoreceptor tyrosine-based activation motif is required for these effects, and we have investigated the involvement of downstream effectors. The ability to up-regulate or down-regulate CR3 signaling has important implications for therapeutics in disorders involving the host defense system.
Department of Hematology/Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. zyh@mail.med.upenn.edu
Zhen-Yu
ZY
Huang
Sharon
S
Hunter
Paul
P
Chien
Moo-Kyung
MK
Kim
Tae-Hee
TH
Han-Kim
Zena K
ZK
Indik
Alan D
AD
Schreiber
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D005260:Female; D006801:Humans; D016177:Macrophage-1 Antigen / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D010766:Phosphorylation; D011485:Protein Binding; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism; D017452:Receptors, IgG / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
D016177:Macrophage-1 Antigen; D051567:Proto-Oncogene Proteins c-vav; D017452:Receptors, IgG