Role of mast cells in plasma permeation due to immune injury of the skin basement membrane.
Immune injury of the basement membrane occurs in various human diseases. In the present study, an antibody specific for the basement membrane of mouse skin was injected i.d. into mast cell-deficient WBB6F1-W/Wv mice and their congenic controls, WBB6F1-(+/+). Vascular permeability changes, oedema and fibrin deposition were assessed. Plasma permeation, evaluated by dye exudation, was time and dose dependent in both groups of animals, but significantly less in WBB6F1-W/Wv than in normal mice. At 30 min, the time of maximum in congenic controls, extravasation of the dye was 60% less in mast cell-deficient than in WBB6F1-(+/+) mice. Pyrilamine decreased exudation by 40% in normal but not in WBB6F1-W/Wv mice, indicating that the mast cell mediator histamine contributes to the increase in vascular permeability. Mast cell deficiency also markedly reduced fibrin deposition as assessed by direct immunostaining. Oedema, measured as skin thickness, was 60% less in WBB6F1-W/Wv mice than in their congenic controls. A 5-lipoxygenase blocker inhibited plasma exudation and oedema in normal but not in WBB6F1-W/Wv mice. This indicates that leukotrienes are involved in these processes and that mast cells are important for their production. Local mast cell reconstitution restored dye extravasation and oedema to normal levels as well as the effect of the 5-lipoxygenase inhibitor. These findings show that mast cells and their mediators participate in these inflammatory processes which were initiated by the deposition of IgG on the skin basement membrane.
Zhang
Y
Y
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri 63110.
Ramos
B F
BF
Jakschik
B A
BA
D000818:Animals; D001327:Autoimmune Diseases / Q000503:physiopathology*; D001485:Basement Membrane / Q000276:immunology / Q000378:metabolism; D002199:Capillary Permeability / Q000502:physiology*; D004487:Edema / Q000503:physiopathology; D005337:Fibrin / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D012867:Skin / Q000378:metabolism*; D012871:Skin Diseases / Q000503:physiopathology
D007074:Immunoglobulin G; D005337:Fibrin