Signal-specific activation and regulation of human neutrophil Fc gamma receptors.
FcgammaRs with the ITIM domain have been shown to regulate the inflammatory signal delivered by the ITAM-containing FcgammaRs. In this study, we demonstrate that the function of human neutrophil FcgammaR type IIA (CD32A) is regulated in a distinct manner by different cell activation signals at the ligand-binding stage. Activation of neutrophils with fMLP up-regulated the ligand-binding function of CD32A, whereas PMA-mediated activation completely abolished ligand binding without altering CD32A expression. Furthermore, PMA treatment also abolished CD16B-dependent ligand binding irrespective of the level of expression. The effect of PMA was cell type specific, because the ligand-binding function of CD32A expressed on cultured cells such as K562 and CHO-CD32A transfectants was not affected by PMA. Interestingly, phorbol 12,13-dibutyrate, another phorbol ester, and IL-8 up-regulated CD32A-dependent ligand-binding function. These results demonstrate that regulation of CD32A-dependent ligand binding in human neutrophils is not only cell type specific but also activation signal specific. Moreover, these results suggest the possibility that signals delivered to neutrophils by various inflammatory stimuli can exert opposing effects on the function of human FcgammaRs, representing a novel inside-out regulatory mechanism of FcgammaR ligand binding.
Nagarajan
Shanmugam
S
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Fifadara
Nimita H
NH
Selvaraj
Periasamy
P
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D016466:CHO Cells; D015936:Complement C5a / Q000502:physiology; D006224:Cricetinae; D004306:Dose-Response Relationship, Immunologic; D004912:Erythrocytes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000502:physiology; D020014:K562 Cells; D007700:Kinetics; D008024:Ligands; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018375:Neutrophil Activation / Q000187:drug effects / Q000276:immunology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology; D017452:Receptors, IgG / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D012756:Sheep / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015703:Antigens, CD; C080568:Fc gamma receptor IIA; D016209:Interleukin-8; D008024:Ligands; D017452:Receptors, IgG; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D013755:Tetradecanoylphorbol Acetate