Fc gamma receptor activation of neutrophils in cryoglobulin-induced leukocytoclastic vasculitis.
OBJECTIVE
The role of Fc gamma receptors (Fc gamma R) in type I cryoglobulinemia was investigated to characterize novel mechanisms of neutrophil activation in the pathogenesis of leukocytoclastic vasculitis.


METHODS
Neutrophils from healthy donors were incubated with purified monoclonal IgG1 kappa cryoglobulin complexes in vitro. Changes in surface antigen expression and mechanisms of intracellular hydrogen peroxide production and calcium release were measured by flow cytometry.


RESULTS
After incubation for 2 hours, surface expression of Fc gamma RI (CD64), CD66, and CD67 was up-regulated; Fc gamma RII (CDw32), Fc gamma RIII (CD16), and LAM-1 were down-regulated. Using solubilized and complexed cryoglobulins, it was demonstrated that complex formation is necessary to induce intracellular H2O2 production and calcium release from intracellular stores. Both H2O2 generation and calcium mobilization could be inhibited by pretreatment with F(ab')2 fragments of monoclonal antibodies (MAb) against Fc gamma RIII. In contrast, Fab fragments of anti-Fc gamma RII MAb failed to block these activations. Neither the cryoglobulin complex-induced production of H2O2 nor the increase in cytoplasmic calcium was affected by treatment with pertussis toxin, which suggests that pertussis toxin-sensitive G proteins are not involved in signal transduction.


CONCLUSIONS
These results indicate that Fc gamma RIII plays a major role in the pathogenesis of leukocytoclastic vasculitis.
Hundt
M
M
Department of Medicine, Hannover Medical School, Germany.
Zielinska-Skowronek
M
M
Schmidt
R E
RE
D000954:Antigens, Surface / Q000097:blood; D003450:Cryoglobulins / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D009113:Muramidase / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D017452:Receptors, IgG / Q000502:physiology*; D018366:Vasculitis, Leukocytoclastic, Cutaneous / Q000139:chemically induced / Q000473:pathology*
D000954:Antigens, Surface; D003450:Cryoglobulins; D017452:Receptors, IgG; D006861:Hydrogen Peroxide; D009113:Muramidase; D019204:GTP-Binding Proteins