Lysis of human arterial smooth muscle cells infected with herpesviridae by peripheral blood mononuclear cells: implications for atherosclerosis.
The cytotoxicity of peripheral blood mononuclear cells (PBMC) to human arterial smooth muscle cells (SMC) infected with cytomegalovirus (CMV) or herpes simplex virus-1 (HSV) was investigated. PBMC were isolated from heparinized blood of healthy donors by Ficoll-Hypaque centrifugation and were tested for cytotoxicity against human SMC or human fibroblast-like (MRC-5) cells infected with CMV or HSV, using the chromium-51 (51Cr) release cytotoxicity assay. Both SMC and MRC-5 cells infected with either CMV (SMC-CMV), (MRC-5-CMV), or HSV (SMC-HSV), (MRC-5-HSV) were lysed by PBMC above background lysis of uninfected SMC cells. Treatment of PBMC with NK-specific monoclonal CD16 antibody and rabbit complement reduced greatly the lysis of SMC, SMC-CMV, and K562 cells, suggesting that lysis of different types of target cell by PBMC was mediated mainly by natural killer (NK) cells. The pattern of natural cytotoxicity against SMC-CMV was different from that against SMC-HSV. Maximum lysis of SMC-CMV was observed at 24 hr postinfection compared to 8 hr postinfection for SMC-HSV. NK reactivity against SMC-CMV increased from 8 to 24 hr postinfection, followed by a gradual decline at 48 and 72 hr. Supernatants generated by culturing SMC-CMV or coculturing SMC-CMV with PBMC enhanced NK cell-mediated lysis of SMC or SMC-CMV. Natural cytotoxic reactivities of PBMC against SMC-CMV or SMC-HSV may occur in vivo. Such reactions could moderate the interaction of these viruses with vascular SMC and could influence the development and/or the progression of atherosclerotic lesions.
Datta
S K
SK
Department of Surgery, Baylor College of Medicine, Houston, Texas 77030.
Tumilowicz
J J
JJ
Trentin
J J
JJ
D001161:Arteriosclerosis / Q000276:immunology*; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D005347:Fibroblasts / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000382:microbiology; D018139:Simplexvirus / Q000276:immunology*