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 l...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2005-05, Vol.174 (9), p.5423-5432
Main Authors: Nagarajan, Shanmugam, Fifadara, Nimita H, Selvaraj, Periasamy
Format: Article
Language:English
Subjects:
Animals
Antigens, CD - biosynthesis
CHO Cells
Complement C5a - physiology
Cricetinae
Dose-Response Relationship, Immunologic
Erythrocytes - immunology
Erythrocytes - metabolism
Humans
Interleukin-8 - physiology
K562 Cells
Kinetics
Ligands
N-Formylmethionine Leucyl-Phenylalanine - pharmacology
Neutrophil Activation - drug effects
Neutrophil Activation - immunology
Neutrophils - drug effects
Neutrophils - immunology
Neutrophils - metabolism
Protein Binding - immunology
Receptors, IgG - antagonists & inhibitors
Receptors, IgG - biosynthesis
Receptors, IgG - metabolism
Sheep - immunology
Signal Transduction - drug effects
Signal Transduction - immunology
Tetradecanoylphorbol Acetate - pharmacology
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.174.9.5423