INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1) IS UP-REGULATED ON ALVEOLAR MACROPHAGES FROM AIDS PATIENTS

In acquired immune deficiency syndrome (AIDS) patients, alveolar macrophages (AMs) have an increased ability to serve as accessory cells during the generation of an immune response. In addition to soluble mediators, like cytokines, molecules of the major histocompatibility complex (MHC) class II and adhesion molecules, like intercellular adhesion molecule-1 (ICAM-1), play a major role in the regulation of these cellular interactions. Using an enzyme-linked immunosorbent assay (ELISA) technique and immunocytochemical staining, we investigated ICAM-1 and human leucocyte antigen-DR (HLA-DR) expression on AMs from 20 AIDS (HIV+) patients in context with other parameters of macrophage activation, such as tumour necrosis factor-alpha (TNF-alpha) secretion and the release of superoxide anion, comparing the results to a group of healthy volunteers. In addition, we quantified soluble ICAM-1 in the bronchoalveolar lavage fluid (BALF) using a commercially available kit. We found a nearly twofold increase in ICAM-1 expression (0.81+/-0.30 (SD) versus 0.42+/-0.12 ELISA units (EU) (mean+/-SD)), whilst the number of HLA-DR+ AMs was slightly decreased in AIDS-patients (80+/-5 versus 89+/-3%). Furthermore, soluble ICAM-1 in the BALF of these patients was significantly increased (41.9+/-26.1 versus 19.1+/-5.1 ng.ml(-1). ICAM-1 levels on AMs in the patient group correlated strongly with the sodium fluoride triggered release of superoxide anion (O-2(-)) but not with the spontaneous secretion of TNF-alpha by AMs. Considering the present knowledge of the role of oxygen radicals in virus replication, increased ICAM-1 expression might reflect the active state of HIV-1 infection of AM in advanced disease. Furthermore, enhanced adhesiveness may facilitate syncytia formation between macrophages and lymphocytes and, thereby, the transfer of HIV-1 to susceptible CD4+ cells, which will ultimately result in a CD4+ cell depletion of the pulmonary compartment.