Yc. Patry et al., Rats injected with syngenic rat apoptotic neutrophils develop antineutrophil cytoplasmic antibodies, J AM S NEPH, 12(8), 2001, pp. 1764-1768
Antineutrophil cytoplasmic antibodies (ANCA) are present in sera from patie
nts with various forms of vasculitis-associated glomerulonephritis. Because
autoantibodies may be directed against antigens presented by apoptotic cel
ls, generation of ANCA using apoptotic neutrophils (PMN) in syngenic Brown
Norway (BN) rats was attempted. These rats are T-helper type 2-prone animal
s, already used successfully in other ANCA-positive animal models. BN rats
received repeated injections of buffer or of nonapoptotic or apoptotic PMN
aged in cultures, in the footpad and once intravenously. Four of five rats
that received injections of PMN aged for 48 h developed ANCA, which cross-r
eacted with human leukocyte elastase in three cases. None of the rats that
received injections of freshly isolated neutrophils developed ANCA. One rat
that received buffer injection and that exhibited chronic skin infection d
eveloped delayed ANCA. None of the rats showed signs of disease: no weight
loss and no proteinuria. Then a subnephritogenic dose of antibody directed
against rat glomerular basement membrane was injected. Rats then were kille
d, and different organs were frozen and studied. No significant lesions wer
e found in kidneys or lungs. It is concluded that injections of apoptotic b
ut not freshly isolated PMN can generate ANCA in BN rats. Additional studie
s are needed to elucidate the immunization mechanism and the ability of the
se autoantibodies to initiate vasculitis in these experimental animals.