Biologically active intercellular adhesion molecule-1 is shed as dimers by a regulated mechanism in the inflamed pleural space.
Intercellular adhesion molecule-1 (ICAM-1) is an adhesion molecule that plays a crucial role in cell-cell interactions involved in the recruitment of cells and immune responses. Under some circumstances, ICAM-1 is found as a soluble protein that has the potential to influence the nature of immunoinflammatory responses. By examining cells and fluid from the pleural compartment of patients with cancer, tuberculosis, and congestive heart failure, the cellular source, conformation, control, and biological activity of soluble ICAM-1 (sICAM-1) were investigated. The results suggest that dimeric sICAM-1 was released locally in the pleural compartment of tuberculous and malignant effusions. sICAM-1 was shed from preexpressed surface ICAM-1 rather than produced de novo, and both CD45-positive leukocytes and cytokeratin-positive epithelial and mesothelial cells expressed ICAM-1, suggesting multiple cellular sources for sICAM-1. The expression of sICAM-1 was regulated because pleural macrophages caused release of sICAM-1 via a tumor necrosis factor-alpha-dependent mechanism. The functional significance of sICAM-1 was demonstrated by showing that pleural sICAM-1 interfered with conjugate formation between LAK cells and K562 cells, suggesting that pleural sICAM-1 plays an immunosuppressive role by inhibiting adhesion of cytotoxic lymphocytes and tumor cells. Thus, sICAM-1 is shed from the surface of cells in a regulated manner and has the potential to influence the immune response in the pleural space.
Melis
Mario
M
Institute of Respiratory Physiopathology, Italian National Research Council, Palermo, Italy.
Pace
Elisabetta
E
Siena
Liboria
L
Spatafora
Mario
M
Tipa
Annalisa
A
Profita
Mirella
M
Bonanno
Anna
A
Vignola
Antonio M
AM
Bonsignore
Giovanni
G
Mody
Christopher H
CH
Gjomarkaj
Mark
M
D000368:Aged; D000369:Aged, 80 and over; D019281:Dimerization; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008175:Lung Neoplasms / Q000276:immunology; D008264:Macrophages; D008297:Male; D008875:Middle Aged; D010996:Pleural Effusion; D010998:Pleurisy / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology
D018799:Intercellular Adhesion Molecule-1