MACROPHAGE-LYSIS MEDIATED BY AUTOANTIBODIES TO HEAT-SHOCK PROTEIN-65 60/

Macrophages in atherosclerotic lesions have been shown to express high amounts of heat shock protein 60 (hsp60), a highly conserved protein. Patients with atherosclerosis have high titers of anti-hsp65/60 antib odies (Ab) recognizing macrophages in the lesions. To elucidate the ro le of anti-hsp65/60 Ab in macrophage cytotoxicity, human high titer se rum and purified anti-hsp65/60 Ab were tested on in vitro heat-stresse d cells of a human macrophage cell line (U937) and macrophages derived from peripheral blood. Application of heat stress at 42 degrees C for 30 min resulted in marked upregulation of hsp60 mRNA, followed by inc reased protein expression as determined by Northern blot and FACS-anal yis, respectively. Compared to unstressed cells, both high titer serum and anti-hsp65/60 Ab preferentially bound to the surface of stressed U937 macrophages, but not control antibodies. Furthermore, high titer serum and anti-hsp65/60 Ab exerted significant (P < 0.01) complement-m ediated cytotoxicity and antibody-dependent cellular cytotoxicity (ADC C) on stressed Cr-51-labelled U937 and peripheral blood derived macrop hages. Thus, macrophages expressing hsp60 can be lysed by autoantibodi es against hsp65/60, which may contribute to cell death in atheroscler otic plaques in vivo. Copyright (C) 1997 Elsevier Science Ireland Ltd.