Roles of tumor necrosis factor-alpha and transforming growth factor-beta in regulating intercellular adhesion...

Profiles of intercellular adhesion molecule-1 (ICAM-1) expression on murine peritoneal macrophages (M phi s) infected with Mycobacterium leprae during cultivation were examined with special reference to the regulatory effects of tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta). When M phi s were infected with M. leprae or stimulated with heat-killed M. leprae at day 0, their ICAM-1 expression, measured in terms of the ratio of M phi s positively stained with anti-ICAM-1 antibody (Ab), rapidly increased, peaking during days 1 to 3 and thereafter fell, returning to the normal level by day 7. The addition of TNF-alpha or anti-TGF-beta Ab inhibited the middle phase (day 7) downregulation of M phi ICAM-1 expression, although the late-phase (day 14) downregulation of ICAM-1 was not prevented by them. M. leprae-infected M phi s released small amounts of TNF-alpha and significant amounts of TGF-beta into the culture medium. This may indicate that M. leprae-infected M phi s produced the majority of TNF-alpha in a membrane-bound form. Alternatively, endogenous TNF-alpha might upregulate M phi ICAM-1 expression even at very low concentrations. In any case, these findings indicate the central roles of TNF-alpha and TGF-beta in the early phase upregulation and the middle-to-late phase downregulation, respectively, of ICAM-1 expression by M. leprae-infected M phi s.