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.