Membrane and soluble forms of Fas (CD95) and Fas ligand in peripheral blood mononuclear cells and in plasma from human immunodeficiency virus-infected persons.
The expression of membrane-bound Fas ligand (FasL) and Fas in lymphocytes and monocytes and levels of soluble forms of FasL (sFasL) and Fas (sFas) in plasma from human immunodeficiency virus (HIV)-positive and -negative subjects was evaluated. Surface FasL was detectable on monocytes, but poorly so on lymphocytes, even in the presence of KB8301, a metalloproteinase inhibitor. Unexpectedly, monocytes of HIV-positive subjects expressed less FasL than those of HIV-negative volunteers. sFasL levels in plasma of HIV-positive persons were elevated and correlated with levels in plasma and with HIV RNA burden. sFas levels in plasma of HIV-positive subjects were also elevated and correlated with Fas expression in apoptotic lymphocytes. Finally, culture-induced lymphocyte apoptosis of HIV-positive subjects was enhanced by anti-Fas agonistic antibody but was not inhibited by anti-FasL blocking antibodies. These results suggest that significant dysregulation of both Fas and FasL occurs in HIV infection and contributes to increased sensitivity of lymphocytes to apoptosis.
Hosaka
N
N
Department of Pediatrics (Division of Allergy/Immunology), North Shore University Hospital-New York University School of Medicine, Manhasset 11030, USA.
Oyaizu
N
N
Kaplan
M H
MH
Yagita
H
H
Pahwa
S
S
D017209:Apoptosis; D053222:Fas Ligand Protein; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology; D008562:Membrane Glycoproteins / Q000097:blood* / Q000235:genetics; D008565:Membrane Proteins / Q000097:blood; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D009000:Monocytes / Q000276:immunology; D011480:Protease Inhibitors; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction; D012995:Solubility; D019014:fas Receptor / Q000097:blood*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011480:Protease Inhibitors; D012333:RNA, Messenger; D019014:fas Receptor; D008666:Metalloendopeptidases