A temporal role for mast cells in the development of adjuvant-induced vasculitis

Rats immunized with Mycobacterium butyricum develop a vasculitis char acterized by increased rolling and adhesion within post-capillary venules [J. Exp. Med. 183:1995-2006]. The objective of this study was to identify the role of perivascular mast cells in the development of adjuvant-induced vasculitis. The mesentery was superfused with ruthenium red, a dye taken up specifically by activated mast cells. Four days after immunization, mesenteric mast cells took up the ruthenium red dye, while dye uptake was not observed twelve days after immunization. Animals were treated with daily oral doses of saline, or the mast cell stabilizer sodium cromoglycate (cromolyn). Four days after immunization, ruthenium red uptake was absent in cromolyn- treated animals. Leukocyte rolling flux and firm adhesion in mesenteric venules was also reduced by 50%. Twelve days after immunization, leukocyte rolling flux and adhesion were not different between the cromolyn-stabilized and saline control groups. However, there was a three-fold increase in the number of emigrated leukocytes in the cromolyn-treated group. These data suggest that mast cells play a role in enhancing leukocyte rolling flux and adhesion during the initiation of the disease state, but by day twelve function to prevent the transmigration of recruited leukocytes.