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 monocytes phagocytic function, oxidative burst, transendothelial migration, and cell surface phenotype.

Abstract

We postulated that changes in the cell surface display of molecules that facilitate cell-cell and cell-matrix adhesions may reflect the changing immunosurveillance capacity of blood monocytes during progression of human immunodeficiency virus (HIV) infections. In Centers for Disease Control (CDC) stage A patients, whose monocytes' ability to phagocytose bacteria and generate reactive oxygen intermediates is often increased, the frequency of monocytes expressing CD49d, HLA-DP, HLA-DQ, and an activation epitope of CD11a/CD18 was increased and monocyte transendothelial migration was unimpaired. In CDC stage B/C patients, whose monocytes' ability to phagocytose bacteria and migrate across confluent endothelial monolayers was diminished, surface expression of CD49e and CD62L and the percentage of monocytes expressing CD18, CD11a, CD29, CD49e, CD54, CD58, CD31, and HLA-I were significantly decreased. Incubating normal donor monocytes with immune complexes in vitro reproduced the phenotypic and functional abnormalities seen in stage B/C patients. By contrast, in vitro stimulation with subcellular particulates released by apoptotic lymphocytes reproduced changes seen in stage A patients' monocytes. Although circulating monocytes appear to be activated at all stages, these data suggest that the high levels of circulating immune complexes, found predominantly in the later stages of HIV infection, may be particularly instrumental in reducing the monocyte's capacity to maintain surveillance against infection. (J. Clin. Invest. 1995. 95:1690-1701

Single-Cell, Phosphoepitope-Specific Analysis Demonstrates Cell Type- and Pathway-Specific Dysregulation of Jak/STAT and MAPK Signaling Associated with In Vivo Human Immunodeficiency Virus Type 1 Infection

“…Expansion of the phospho-flow screen to include other phospho-proteins activated by GM-CSF led to the observation that LPS-stimulated ERK phosphorylation was enhanced in HIV-1 infection. Reduced signaling potential of "antiviral" STAT pathways, and enhanced signaling of "inflammatory" MAPK pathways are consistent with long-standing observations of monocyte dysfunction in HIV-1 infection, including reduced antigen uptake and hyperactive inflammatory cytokine secretion (5,39). These results provide a specific molecular basis for the prior observations of dysfunction.…”

Modulation of the effector function of human macrophages for Histoplasma capsulatum by HIV-1. Role of the envelope glycoprotein gp120.

“…Monocytes from asymptomatic HIVϩ individuals have been found to have increased levels of CD11a, CD11b, and CD11c (41,42). Others have demonstrated decreased levels of CD11a on monocytes and alveolar M from AIDS patients (40).…”

Monocyte Activation by Circulating Fibronectin Fragments in HIV-1-Infected Patients

“…This hypothesis is supported by in vitro studies of the effect of antiretrovirals on infected monocytes (7,8) and by reports that HAART improves patients' leukocyte function in vivo (9). Although the agents that cause these leukocyte function defects remain poorly characterized, viral proteins, debris from apoptotic leukocytes, soluble immune complexes, and activated complement fragments have all been implicated (3,7,10). In the pre-HAART era, circulating soluble Ag-Ab complexes, in particular, appeared to be responsible for the decline in monocyte phagocytic function.…”

“…B efore highly active antiretroviral therapy (HAART), 3 leukocyte functions declined significantly during the progression of HIV-1 infections (1-3). As the disease continues, leukocyte phagocytic activity, which is normal or even enhanced in asymptomatic (stage A) patients (1, 2), becomes defective (3) as do monocyte chemotactic responses, oxidative burst, and transendothelial migration (3)(4)(5).…”

“…As the disease continues, leukocyte phagocytic activity, which is normal or even enhanced in asymptomatic (stage A) patients (1, 2), becomes defective (3) as do monocyte chemotactic responses, oxidative burst, and transendothelial migration (3)(4)(5). By reducing viral burden (6), HAART may remove stimuli that alter leukocyte functions.…”