Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:The glycosylphosphatidylinositol-linked Fc gamma receptor III represents the dominant receptor structure for immune complex activation of neutrophils. 153 49

Leukoclastic vasculitis is thought to be initiated by deposition of immune complexes (ICs) in the vascular wall. To study the neutrophil response in a related in vitro model, we primed human umbilical vein endothelial cell (HUVEC) monolayers with antibodies against human fibronectin. The resulting respiratory burst to the immobilized ICs depended on the antibody concentration used to prime the monolayers and included a marked release of primary and secondary granule constituents. On IC-bearing HUVEC monolayers, but not on ICs directly bound to tissue culture dishes, blocking monoclonal antibodies (mAbs) to crystallizable fragment-gamma receptor II (Fc gamma RII) and Fc gamma RIII markedly inhibited the respiratory burst and the release of elastase. However, on both surfaces the neutrophil response was strongly inhibited by mAbs against CD18. Regardless of whether we used neutrophils from a patient with severe paroxysmal nocturnal hemoglobinuria (PNH) lacking the Fc gamma RIII, or whether the Fc gamma RII-mediated signal transduction was blocked by pertussis toxin, the respiratory burst to the IC-bearing HUVECs was essentially unchanged. With PNH neutrophils, the respiratory burst was predominantly blocked by an anti-Fc gamma RII mAb. In contrast, the response of pertussis toxin treated neutrophils was strongly inhibited by a mAb against Fc gamma RIII. Together these data indicate that the answer of neutrophils to ICs immobilized at the endothelial barrier depends on the cooperative function of both low-affinity Fc gamma Rs.
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PMID:Neutrophil activation in response to immune complex-bearing endothelial cells depends on the functional cooperation of Fc gamma RII (CD32) and Fc gamma RIII (CD16). 749 May 18