Shed soluble ICAM-1 molecules in bronchoalveolar lavage cell supernatants and serum of patients with pulmonary sarcoidosis

Abstract

The soluble form of intercellular adhesion molecule-1 (sICAM-1) might be a serum parameter of inflammatory activity gauging cellular interactions with possible relevance in sarcoidosis. To address this question we measured sICAM-1 by enzyme-linked immunosorbent assay in serum and shedding of this molecule by bronchoalveolar lavage (BAL) cells in sarcoidosis patients (44 and 40, respectively) and in controls (10 and 19, respectively). Serum concentrations of sICAM-1 (588.3 +/- 72.2 ng/ml) and its spontaneous release by BAL cells (9.9 +/- 1.5 ng/ml) in patients with active sarcoidosis were significantly higher than in those with inactive disease or controls, although no correlation was observed. Significant correlations of sICAM-1 shedding by nonstimulated BAL cells with the serum level of neopterin and of shedding by lipopolysaccharide-stimulated BAL cells with percentage of alveolar macrophages were observed in active sarcoidosis. Kinetic cell culture experiments with peripheral blood mononuclears disclosed a rapid up-regulation of sICAM-1 shedding and tumor necrosis factor-alpha release; however, at 5 h after stimulation a dissociation of their releases was observed. sICAM-1 release was maintained over 2 days, whereas tumor necrosis factor-alpha release peaked at 5 and ceased after 43 h. These results provide evidence that circulating and BAL cell culture-derived sICAM-1 reflect the stage of sarcoid inflammation. Although sICAM-1 in BAL cell supernatants originates from alveolar macrophages; the absence of a correlation with serum sICAM-1 concentration indicates that other cells are additional sources of the circulating pool of this molecule.