ROLE OF NEUTROPHILS IN THE PATHOGENESIS OF EXPERIMENTAL VASCULITIS

Citation
Fj. Qasim et al., ROLE OF NEUTROPHILS IN THE PATHOGENESIS OF EXPERIMENTAL VASCULITIS, The American journal of pathology, 149(1), 1996, pp. 81-89
Citations number
40
Categorie Soggetti
Pathology
ISSN journal
00029440
Volume
149
Issue
1
Year of publication
1996
Pages
81 - 89
Database
ISI
SICI code
0002-9440(1996)149:1<81:RONITP>2.0.ZU;2-M
Abstract
In the Brown-Norway rat, mercuric chloride (HgCl2) induces an autoimmu ne syndrome characterized by high IgE levels. There is widespread necr otizing leukocytoclastic vasculitis involving lung, skin, mucous membr anes, pancreas, liver, and gut, with tissue injury being most marked i n the cecum. As in systemic vasculitis in man, there are neutrophils a t the site of tissue injury and the animals develop anti-neutrophil cy toplasmic antibodies, which in the Brown-Norway rat are directed again st myeloperoxidase. To determine whether neutrophils are involved in t he pathogenesis of the vasculitis, we have used a monoclonal antibody that was reported to deplete neutrophils in other rat strains. Rats tr eated with HgCl2 received antibody by intravenous injection at various time points. Serial blood samples were taken for neutrophil counts an d to assay for anti-myeloperoxidase and IgE antibodies. The guts of an imals killed after antibody therapy were scored for vasculitic changes and neutrophil infiltrate. RP3 (but not the control antibody MAC6) wa s shown to bind to Brown-Norway rat neutrophils and to block glycogen- induced influx of neutrophils into the peritoneum. When given at peak disease, RP3 caused a dose-dependent reduction in tissue injury with a marked reduction in circulating blood neutrophil numbers and in tissu e neutrophil infiltrate. RP3 treatment did not affect the rise in tite r of IgE and anti-myeloperoxidase antibodies. The data presented demon strate that in this model neutrophils are necessary for the induction of vasculitis and that the degree of vasculitis correlates with neutro phil number. To our knowledge, this study is the first to provide dire ct evidence for a role for neutrophils in vasculitis. We suggest that antibodies directed against neutrophils, especially they deplete neutr ophils, may be useful in the therapy of vasculitis in man.