title: Mast cell mediators regulate vascular permeability changes in Arthus reaction.
abstract: Plasma exudation characterizes the early phase of acute inflammation. The possible role of mast cells and their mediators in this event in immune complex-induced injury was studied. Dye exudation was assessed from 5 min to 2 hr after initiating reverse passive Arthus reaction in mast cell-deficient mice, WBB6F1-W/Wv (W/Wv), and their normal congenic controls, WBB6F1-+/+ (+/+). The response to antibody (10, 30 and 100 micrograms/site, i.d.) was dose- and time-dependent in both groups of mice. At the lower doses of antibody, 10 and 30 micrograms/site, exudation was significantly less (30% and 40%, respectively) in W/Wv as compared to +/+ mice between 15 to 45 min. With 100 micrograms of antibody/site, significant differences between W/Wv and +/+ mice were noted only at 15 and 30 min. The deficit in permeability changes in W/Wv mice was reversed by local mast cell reconstitution. In +/+ mice, pyrilamine and methysergide pretreatment reduced vascular permeability to the same extent by 70, 60 and 35% when stimulated for 30 min with 10, 30 and 100 micrograms of antibody/site, respectively. An equivalent inhibition was observed with the 5-lipoxygenase inhibitor A-63162. None of the inhibitors decreased plasma permeation in W/Wv mice. These results indicate that the mast cell mediators histamine and serotonin regulate vascular permeability early during an immune complex-mediated inflammation. The data also suggest the involvement of leukotrienes and the importance of mast cells in their synthesis. The profile of inhibition in +/+ mice agrees well with the difference in exudation observed between normal and mast cell-deficient mice.
authors.affiliation: Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: B F
authors.initials: BF
authors.lastname: Ramos
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: V
authors.initials: V
authors.lastname: Angkachatchai
authors.forename: B A
authors.initials: BA
authors.lastname: Jakschik
mesh_terms: D000818:Animals; D001183:Arthus Reaction / Q000503:physiopathology*; D002199:Capillary Permeability; D015550:Cell Degranulation; D015289:Leukotrienes / Q000494:pharmacology; D008407:Mast Cells / Q000502:physiology*; D051379:Mice
chemical_list: D015289:Leukotrienes