Mast cells enhance the antibody-mediated injury of skin basement membrane in mice.
Immunologic basement membrane injury occurs in certain human diseases. We investigated the role of mast cells in the initiation of inflammation induced by selective deposition of antibody on the basement membrane in the skin. Intradermal injection of the antibody into mast cell-deficient WBB6F1-W/Wv mice and their congenic controls, WBB6F1-+/+, caused C (C3) deposition and tissue damage preferentially at the dermo-epidermal junction (basement membrane). Damage occurred earlier and was more extensive in normal than in WBB6F1-W/Wv mice. Hemorrhage in WBB6F1-W/Wv was reduced by 50%. In both groups of mice, a dose- and time-dependent neutrophil infiltration reached maximum at 8 h. At the peak, neutrophil accumulation in WBB6F1-W/Wv was only 50% of that in normal mice. Mast cell reconstitution of WBB6F1-W/Wv mice normalized the inflammatory response. Pretreatment with a 5-lipoxygenase inhibitor, A-63162, reduced neutrophil infiltration by 60% in normal but not in WBB6F1-W/Wv mice. Mast cell repletion restored the effect of A-63162. The results indicate that mast cells are important for the initiation of inflammation induced by the deposition of antibody on the basement membrane and the production of leukotrienes participating in neutrophil elicitation.
Zhang
Y
Y
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110.
Ramos
B F
BF
Jakschik
B A
BA
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000276:immunology; D001485:Basement Membrane / Q000473:pathology; D015550:Cell Degranulation; D003872:Dermatitis / Q000209:etiology; D007249:Inflammation / Q000209:etiology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D009504:Neutrophils / Q000502:physiology; D012867:Skin / Q000276:immunology*
D000906:Antibodies; D000936:Antigen-Antibody Complex; D016859:Lipoxygenase Inhibitors