Pathogenesis of arteritis of SL/Ni mice. Possible lytic effect of anti-gp70 antibodies on vascular smooth muscle cells.
The SL/Ni strain of mice spontaneously develops a necrotizing polyarteritis (NPA) that is histologically quite similar to human polyarteritis nodosa. This NPA most frequently affected parametrial tissues and/or ovaries of females and small arterioles of the major salivary glands. Electron microscopic studies of early arterial lesions revealed massive budding of C-type particles from arterial smooth muscle cells just before or at the onset of arteritis. In addition, binding of mouse IgG and C3 to the plasma membrane of virus-producing smooth muscle cells was shown by immunoelectron microscopy. Antibody-bound muscle cells showed disintegration of their plasma membrane, but degeneration and necrosis of muscle cells were not associated with dense infiltration of neutrophils. SL/Ni mice had natural antibodies that bound specifically to a fibroblast cell line infected with an endogenous ecotropic murine leukemia virus (MuLV) recovered from a SL/Ni mouse. Most of the natural antibodies were cytotoxic in the presence of murine complement. Western blot immunoassays revealed that among 14 SL/Ni female mice tested, all of the 9 mice that were affected by arteritis had anti-gp70 antibodies, while the 3 anti-gp70- mice were not affected. The presence of anti-p30 or anti-p15 (anti-p12) antibodies, which were also detected in some SL/Ni mice, did not correlate with the development of arteritis. These results strongly support the hypothesis that NPA in SL/Ni mice is mediated by the lysis of arterial smooth muscle cells due to the deposition of cytotoxic natural antibodies directed to cell membrane-bound gp70 molecules of an endogenous ecotropic MuLV.
D000818:Animals; D000906:Antibodies; D001167:Arteritis / Q000209:etiology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D009131:Muscle, Smooth, Vascular / Q000276:immunology*; D010488:Polyarteritis Nodosa / Q000209:etiology; D012191:Retroviridae Proteins / Q000276:immunology*; D015682:Retroviridae Proteins, Oncogenic; D014759:Viral Envelope Proteins / Q000276:immunology*; D014771:Virion / Q000032:analysis
D000906:Antibodies; D012191:Retroviridae Proteins; D015682:Retroviridae Proteins, Oncogenic; D014759:Viral Envelope Proteins