The glycosylphosphatidylinositol-linked Fc gamma receptor III represents the dominant receptor structure for immune complex activation of neutrophils.
Polymorphonuclear neutrophils (PMN) express constitutively two low-affinity Fc gamma receptors, Fc gamma RII and Fc gamma RIII. Fc gamma RII is a transmembrane molecule, and Fc gamma RIII is linked via a glycosylphosphatidylinositol (GPI) anchor to the membrane. The role of each of these receptors in activation of PMN is still unclear. We used specific cross-linking of Fc gamma RII via Fab fragments of IV.3 (anti-Fc gamma RII, CDw32) and of Fc gamma RIII using F(ab')2 fragments of 3G8 (anti-Fc gamma RIII, CD16) to activate PMN. Stimulation of Fc gamma RIII was significantly more effective in inducing a respiratory burst than cross-linking of Fc gamma RII. A synergistic effect was observed after simultaneous activation of Fc gamma RIII. We could demonstrate that both Fc gamma R mobilize calcium as intracellular signal in spite of their different membrane linkage. The kinetic of calcium mobilization after Fc gamma R stimulation is delayed in comparison to formyl-methionyl-leucyl-phenylalanine activation. In addition Fc gamma R-induced increase of cytoplasmic calcium is pertussis toxin insensitive. When monoclonal IgG1 kappa complexes were used for stimulation calcium mobilization and hydrogen peroxide (H2O2) production could also be demonstrated. Inhibition studies of this activation using monoclonal antibodies suggested that this immune complex activation was predominantly mediated via Fc gamma RIII. Only in Fc gamma RIII-deficient PMN from paroxysmal nocturnal hemoglobinuria patients could a decreased H2O2 production be demonstrated to be Fc gamma RII dependent. In normal PMN the GPI-anchored Fc gamma RIII structure is the predominant receptor.
Hundt
M
M
Abteilung Immunologie und Transfusionsmedizin, Medizinische Hochschule, Hannover, FRG.
Schmidt
R E
RE
D000936:Antigen-Antibody Complex / Q000276:immunology*; D000943:Antigens, Differentiation / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D006017:Glycolipids / Q000032:analysis*; D017261:Glycosylphosphatidylinositols; D006457:Hemoglobinuria, Paroxysmal / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D037342:Pertussis Toxin; D010716:Phosphatidylinositols / Q000032:analysis*; D011961:Receptors, Fc / Q000502:physiology*; D017452:Receptors, IgG; D015398:Signal Transduction; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000936:Antigen-Antibody Complex; D000943:Antigens, Differentiation; D006017:Glycolipids; D017261:Glycosylphosphatidylinositols; D007074:Immunoglobulin G; D010716:Phosphatidylinositols; D011961:Receptors, Fc; D017452:Receptors, IgG; D010566:Virulence Factors, Bordetella; D009240:N-Formylmethionine Leucyl-Phenylalanine; D037342:Pertussis Toxin; D002118:Calcium