Mast cells contribute to fibrin deposition in reverse passive Arthus reaction in mouse skin

The activation of the clotting system is an important process during inflammation to contain the injury and initiate tissue repair. In the present study, we investigated the effect of mast cells on fibrin deposition in reverse passive Arthus reaction in mast cell-deficient WBB6F1-W/Wv(W/Wv) and control WBB6F1-(+)/+(+/+) mice, that were given 125I-labeled fibrogen intravenousty. An antibody dose-dependent increase in radioactivity was observed in the challenged skin sites. Sequential water and urea extractions characterized the radioiodinated fibrinogen derivatives present in the tissue. The radioactivity found in the various fractions of the stimulated samples from +/+ was 2-10-fold higher than that in specimens from W/Wv mice. The greatest difference was observed in the urea-insoluble pellet (cross-linked fibrin and its early degradation products). Reconstitution of W/Wv mice with mast cells augmented the response to levels similar to those in +/+ mice. Pretreatment with the antihistamine pyrilamine blocked the accumulation of 125I-labeled fibrinogen and its derivatives by approximately 70% in +/+ but not in W/Wv mice. Inhibition of leukotriene synthesis by A-63162 markedly decreased the accumulation of iodinated fibrinogen in both +/+ and W/Wv mice. The data suggest that mast cells and their vasoactive mediator histamine contribute to the exudation of clotting factors, which results in fibrin deposition and that mast cells also enhance fibrin cross-linkage.