Monocyte-derived macrophage function in HIV-infected subjects: in vitro modulation by rIFN-gamma and rGM-CSF.
We investigated monocyte-derived macrophage function in 25 HIV-positive patients, 19 in the CDC class III and 6 class IV; 17 were intravenous drug abusers (IVDA) and 8 were homosexual men. Macrophages from HIV-positive patients behaved normally in assays of superoxide anion (O2-) production and candidacidal activity. After 3 days' treatment with 200 U/ml recombinant interferon-gamma (rIFN-gamma) or 250 U/ml recombinant granulocyte/macrophage-colony stimulating factor (rGM-CSF), both control and HIV-positive patients' phagocytes expressed the activated state, as indicated by the increased O2- production in response to phagocytable or soluble stimuli; however, these cytokines did not enhance candidacidal activity. Compared to appropriate HIV-negative controls (18 healthy heterosexuals, 4 homosexuals and 4 IVDA), macrophages from 19 of the 25 HIV-positive patients presented a significant defect in their Fc receptor (FcR)-dependent phagocytosis, independently from the CDC stage, AZT therapy, or life style. Treatment of macrophages with rIFN-gamma impaired their capacity to ingest IgG-coated erythrocytes, both in controls and HIV-positive subjects. Treatment of phagocytes with rGM-CSF significantly increased their FcR-dependent phagocytosis in controls, whereas in HIV-positive patients and in HIV-negative homosexuals and IVDA only an upward tendency was observed. Although the mechanism of the impaired FcR-dependent phagocytosis in HIV-positive patients remain to be clarified, our results suggest that this functional defect may be secondary to phagocyte priming by circulating IFN-gamma in vivo. This macrophage alteration may be implicated in the immunodeficiency of HIV-positive patients. However, considering the potential role of FcRs in HIV infection enhancement, the defective FcR function might even be a protective mechanism against FcR-mediated HIV dissemination. In the light of these findings, the immunotherapeutic potential of IFN-gamma and GM-CSF in HIV infection merits further investigation.
Capsoni
F
F
Instituto di Medicina Interna, Malattie Infettive e Immunopatologia, University of Milan, Italy.
Minonzio
F
F
Ongari
A M
AM
Rizzardi
G P
GP
Lazzarin
A
A
Zanussi
C
C
D000163:Acquired Immunodeficiency Syndrome / Q000503:physiopathology; D000328:Adult; D001790:Blood Physiological Phenomena; D002175:Candida; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D015658:HIV Infections / Q000276:immunology*; D006679:HIV Seropositivity / Q000503:physiopathology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008264:Macrophages / Q000502:physiology*; D008297:Male; D010587:Phagocytosis; D011961:Receptors, Fc / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D016897:Respiratory Burst / Q000276:immunology
D011961:Receptors, Fc; D011994:Recombinant Proteins; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor