Protein kinase C and intracellular free Ca++: relationship to human immunodeficiency virus (HIV)-induced cellular hyporesponsiveness.
Protein Kinase C (PKC) and Ca++ are both involved in the chain of events leading to T-cell activation. An impairment of the immune response is characteristic of T cells obtained from patients with HIV infection. In this report, the involvement of PKC and Ca++ in HIV-mediated cellular hyporesponsiveness was examined. Infection of peripheral blood mononuclear cells (PBMC)s from HIV-seronegative normal donors with HIV strain HTLV IIIB, or two fresh patient isolates produced a 1.4-, 10.7-, and 11.4-fold enhancement in PKC activity at 1 hr postinfection (PI) and a 1.8-, 2.3-, and 3.8-fold enhancement at 12 hr PI, respectively. A marked decrease of PKC content, as determined by Western Blot analysis, was observed in HIV-infected cells by Day 4 and 7 PI compared with mock-infected control cells. Furthermore, PKC synthesis was also inhibited in cells from immunosuppressed AIDS patients. PKC activity of PBMCs from HIV-infected patients did not change in response to 1 microM of phorbal myristate acetate (PMA). In contrast, the same dose enhanced the activity by 50%-100% in PBMCs from normal HIV-seronegative donors. A 40%, 50%, and 125% increase in intracellular free Ca++ in response to HIV infection was observed 12 hr PI in MT4, JURKAT, and PBMCs, respectively. However, the increase in intracellular free Ca++ in HIV-infected PBMCs obtained from normal donors in response to PHA was 56% and 17% compared with an increase of 100% and 120% in mock infected cells at 12 hr and 1 week PI, respectively. Comparing the Ca++ response to PHA in PBMCs from HIV-infected patients showed that patients with < 250 absolute T4 cells/mm3 had an impaired Ca++ response. These data suggest that there is a relationship between intracellular free Ca++ and PKC and HIV-induced T-cell hyporesponsiveness.
Nokta
M A
MA
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555.
Hassan
M I
MI
Morgan
J A
JA
Loesch
K A
KA
Pollard
R B
RB
D002118:Calcium / Q000502:physiology*; D002460:Cell Line; D004789:Enzyme Activation; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation; D011493:Protein Kinase C / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015759:Ionomycin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium