EXPRESSION OF INTERCELLULAR-ADHESION MOLECULE-1 BY MURINE MACROPHAGE IS UP-REGULATED DURING DIFFERENTIATION AND INFLAMMATORY ACTIVATION

Intercellular adhesion molecule-1 (ICAM-1, CD54) is a cell-surface glycoprotein which has been shown to play an important role for cell/cell interaction. Little is known about its occurrence in the murine monocyte/macrophage (MPHI)) lineage; hence, we analyzed ICAM-1 expression in cells and cell lines representing different stages of MPHI maturation and studied its regulation during inflammatory activation. Flow cytometric analysis of bone marrow-derived MPHI cultured in the presence of M-CSF, of thioglycollate-elicited peritoneal MPHI and of M1 myeloblasts differentiated by lipopolysaccharide (LPS) treatment revealed that ICAM-1 is increasingly expressed during monocytic maturation. Accordingly, the myelomonocytic cell lines RMB.TG, WEHI.TG, J774A and P388D, which can be ordered in a linear differentiation sequence, showed increasing levels of ICAM-1 expression. Furthermore, ICAM-1 expression by bone marrow-derived MPHI could be up-regulated by tumor necrosis factor-alpha, interferon-gamma and LPS. In two models of murine experimental inflammation. i.e. induction phase of contact hypersensitivity and cutaneous leishmaniasis, which are both dependent on MPHI/T cell interaction, MPHI expressing ICAM-1 were found to be highly abundant. In addition, it was demonstrated that co-culture of Leishmania major parasites with bone marrow MPHI led to up-regulation of ICAM-1 on these cells. In conclusion, our data clearly demonstrate that ICAM-1 is increasingly being expressed during maturation of murine MPHI. Cytokines and inflammatory stimuli modulate MPHI ICAM-1 expression as well thus referring to its considerable role during inflammation, e.g. providing accessory or costimulatory signals for T cell activation.