PHENOTYPIC AND FUNCTIONAL-CHANGES IN PERIPHERAL-BLOOD MONOCYTES DURING PROGRESSION OF HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION - EFFECTS OF SOLUBLE IMMUNE-COMPLEXES, CYTOKINES, SUBCELLULAR PARTICULATES FROM APOPTOTIC CELLS, AND HIV-1-ENCODED PROTEINS ON MONOCYTE PHAGOCYTIC FUNCTION, OXIDATIVE BURST, TRANSENDOTHELIAL MIGRATION, AND CELL-SURFACE PHENOTYPE

We postulated that changes in the cell surface display of molecules th at facilitate cell-cell and cell-matrix adhesions may reflect the chan ging immunosurveillance capacity of blood monocytes during progression of human immunodeficiency virus (HIV) infections, In Centers for Dise ase Control (CDC) stage A patients, whose monocytes' ability to phagoc ytose bacteria and generate reactive oxygen intermediates is often inc reased, the frequency of monocytes expressing CD49d, HLA-DP, HLA-DQ, a nd an activation epitope of CD11a/CD18 was increased and monocyte tran sendothelial migration was unimpaired, In CDC stage B/C patients, whos e monocytes' ability to phagocytose bacteria and migrate across conflu ent endothelial monolayers was diminished, surface expression of CD49e and CD62L and the percentage of monocytes expressing CD18, CD11a, CD2 9, CD49e, CD54, CD58, CD31, and HLA-I were significantly decreased. In cubating normal donor monocytes with immune complexes in vitro reprodu ced the phenotypic and functional abnormalities seen in stage B/C pati ents, By contrast, in vitro stimulation with subcellular particulates released by apoptotic lymphocytes reproduced changes seen in stage A p atients' monocytes, Although circulating monocytes appear to be activa ted at all stages, these data suggest that the high levels of circulat ing immune complexes, found predominantly in the later stages of HIV i nfection, may be particularly instrumental in reducing the monocyte's capacity to maintain surveillance against infection.