In the Brown Norway rat,
mercuric chloride (
HgCl2) induces an autoimmune syndrome characterized by necrotizing
vasculitis, predominantly affecting the caecum, and a polyclonal B-cell response. The time course of
vasculitis is biphasic, with an alphabeta T-cell independent phase occurring within 24 h, and a T-cell and neutrophil dependent phase, maximal at two weeks. The pathogenesis of the early phase of
vasculitis is unclear, and this study aims to examine the role of neutrophils. Rat neutrophils were depleted using
cyclophosphamide. RP3, an antirat neutrophil
monoclonal antibody, inhibited neutrophil leucocytosis but did not deplete neutrophils.
Vasculitis was induced by subcutaneous
HgCl2 injection. Serial measurements of peripheral blood leucocyte count were made. Rats were killed after 24 or 72 h. The macroscopic appearance of the caecum was scored by an experienced observer, and samples taken for histological examination. Caecums were excised and
myeloperoxidase, a marker
enzyme for neutrophil infiltration, assayed.
Cyclophosphamide induced marked neutropaenia whereas RP3 inhibited the neutrophilia observed after
HgCl2 injection.
Vasculitis was present in both treated and control animals, with no significant differences in macroscopic or microscopic scores between the groups. Tissue
myeloperoxidase activity was low in all animals and did not differ significantly between groups. The data do not support a role for neutrophils in the initial pathogenesis of
vasculitis in this model.