Insoluble immune complex-stimulated neutrophil leukotriene B4 production is dependent on Fc gamma RII and Fc gamma RIII and independent of pertussis toxin-sensitive signal transduction pathways.
Leukotriene B4 (LTB4) release initiated by interaction of immune complexes (ICs) with Fc gamma RII and Fc gamma RIII receptors on human neutrophils was studied using well-defined complexes. Immune complexes consisting of polyclonal rabbit antibody to human albumin were prepared at equivalence (insoluble complex) and at five times antigen excess (soluble complex). Incubation of human neutrophils with soluble and insoluble ICs led to the synthesis of LTB4 from endogenous arachidonic acid (AA). LTB4 release induced by ICs was markedly inhibited by monoclonal antibodies against either Fc gamma RII or Fc gamma RIII receptor. Treatment of neutrophils with pertussis toxin significantly inhibited the release of LTB4 induced by soluble ICs. However pertussis toxin treatment minimally inhibited the LTB4 release induced by insoluble ICs. Crosslinking of either Fc gamma RII and Fc gamma RIII receptors on neutrophil surfaces induced LTB4 release. This is the first experimental observation showing that both Fc gamma RII and Fc gamma RIII directly induce neutrophil LTB4 metabolism in the absence of exogenous AA. These studies also suggest the involvement of novel pertussis toxin insensitive signal transduction pathways in insoluble ICs stimulation of neutrophils.
Crockett-Torabi
E
E
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602.
Smith
C W
CW
Kateley
J R
JR
Patterson
R
R
Tsai
P
P
Fantone
J C
JC
D000936:Antigen-Antibody Complex / Q000502:physiology*; D003432:Cross-Linking Reagents / Q000494:pharmacology; D006801:Humans; D007975:Leukotriene B4 / Q000096:biosynthesis*; D009504:Neutrophils / Q000378:metabolism*; D037342:Pertussis Toxin; D011961:Receptors, Fc / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D012995:Solubility; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D000936:Antigen-Antibody Complex; D003432:Cross-Linking Reagents; D011961:Receptors, Fc; D010566:Virulence Factors, Bordetella; D007975:Leukotriene B4; D037342:Pertussis Toxin