Functional association of FcepsilonRIgamma with arginine(632) of paired immunoglobulin-like receptor (PIR)-A3 in murine macrophages.
Paired immunoglobulin-like receptors (PIR) are expressed on B cells and macrophages and include inhibitory and putative activating receptors referred to as PIR-B and PIR-A, respectively. Although PIR-B's inhibitory pathway has been described, it is unknown whether PIR-A receptors can deliver activation signals to macrophages, and if so, through what mechanism. Here we use chimeric receptors to address the mechanisms of PIR-A signaling. Cotransfection of chimeric receptors comprised of the extracellular region of human CD4 and the transmembrane and cytoplasmic domains of murine PIR-A3 showed the ability of PIR-A3 to physically interact with the FcepsilonRIgamma chain in 293T cells. This interaction is dependent on Arg(632) within the PIR-A3 transmembrane domain. We also demonstrate PIR-A3 interaction with the endogenous FcepsilonRIgamma of the ANA-1 macrophage cell line, again in an Arg(632)-dependent manner. Furthermore, we show that crosslinking of these chimeric receptors synergizes with IFN-gamma in the production of nitric oxide. Our data are the first to show the potential of PIR-A3 to deliver activation signals to macrophages and establish its dependence on Arg(632). These findings suggest that further study of the PIR-A receptors should be aggressively pursued toward a complete understanding of the intricate regulation of macrophage biology.
Taylor
L S
LS
Laboratory of Experimental Immunology, Division of Basic Sciences, National Cancer Institute, NCI-FCRDC, Frederick, MD 21702, USA.
McVicar
D W
DW
D000818:Animals; D001120:Arginine; D002478:Cells, Cultured; D006801:Humans; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D011940:Receptor Aggregation; D017455:Receptors, IgE / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction
C105948:Pira1 protein, mouse; D017455:Receptors, IgE; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; D001120:Arginine