Cytotoxicity of activated monocytes on endothelial cells
Peri, G.; Chiaffarino, F.; Bernasconi, S.; Padura, I.M.; Mantovani, A.
Journal of Immunology 144(4): 1444-1448
1990
ISSN/ISBN: 0022-1767 PMID: 2137492 Document Number: 365915
Unstimulated human monocytes did not express appreciable levels of cytotoxicity on normal human umbilical vein endothelial cells (EC) in a 24-48 hr TdR release assay. On activation with IFN-.gamma. and LPS, monocytes had a appreciable cytotoxicity on EC. Monocyte cytotoxicity on EC was not dependent on the presence of contaminating lymphoid cells. Recombinant TNF, IL-1, and IL-6 as well as monocyte supernatants did not exert a cytotoxic effect on EC. Moreover, anti-TNF, anti-IL-1, and anti-IL-6 antibodies, as well as scavengers of reactive oxygen intermediates, did not affect the cytotoxicity of activated monocytes on EC. Antibodies against the .beta.-chain (CD18) of leukocyte integrins inhibited the adhesion and cytotoxicity of activated monocytes on EC. Pretreatment of EC with IL-1 augmented the adhesion of monocytes on EC. Normal monocytes were not cytotoxic on IL-1-pretreated EC and IL-1 treatment did not increase the susceptibility of EC to activated monocytes. Thus adhesion is necessary but not sufficient for monocyte killing of EC. Anti-.alpha.L (LFA-1) antibodies markedly reduced monocyte cytotoxicity on EC, although anti-.alpha.X (p150) antibodies had only a modest effect. Anti-.alpha.M (Mac-1/CR3) antibodies were intermediate inhibitors of EC killing by activated monocytes. Thus, .alpha.L, .beta.2 (LFA-1), and, to a lesser extent, .alpha.M, .beta.2 (Mac-1/CR3) and .alpha.X, .beta.2 (p 150, 95) integrins are the main adhesive structures involved in the cytotoxic interaction of activated monocytes with EC. Monocyte-mediated damage of EC could play a role as a mechanism of tissue injury under conditions of local or systemic activation of mononuclear phagocytes.