LIPOPOLYSACCHARIDE-INDUCED DIFFERENTIAL CELL SURFACE EXPRESSION OF INTERCELLULAR ADHESION MOLECULE-1 IN CULTURED HUMAN UMBILICAL CORD VEIN ENDOTHELIAL CELLS

The effect of endotoxin on cell surface ICAM-1 expression in human umbilical cord vein endothelial cells (HUVEC) was examined using solid phase radioimmunoassay, immunocytochemistry and electron microscopy. At various incubation times (e.g. 3, 6, 12, 24 h), the ICAM-1 expression was enhanced by lipopolysaccharide (LPS, or endotoxin) from one ng/ml to 100 micrograms/mL with maximal enhancement at .1-1 micrograms/mL. The kinetics at 1 microgram/mL LPS showed that the maximum ICAM-1 expression occurred at 24 h. The LPS-induced ICAM-1 expression was not inhibited by the neutralizing rabbit polyclonal antibodies against human IL-1 alpha, IL-1 beta, and TNF alpha, either alone or in combination. This indicated that the mechanism of this induced expression was not an autocrine effect mediated by the LPS-induced IL-1 or TNF alpha. The LPS-induced cell surface ICAM-1 exhibited a polarized distribution shown in immunoelectron micrographs with higher density on the luminal surface. DNA synthesis activity of HUVEC was, contrary to the ICAM-1 expression, suppressed by LPS. Immunocytochemical studies indicated that ICAM-1 was not uniformly expressed in the culture, i.e., some cells expressed more surface ICAM-1 than others, and some of the ICAM-1-expressing cells had an uneven patchy distribution of this antigen. Combined immunocytochemical and [3H]thymidine incorporation studies showed that cells with strong ICAM-1 expression had little DNA synthesis activity, while those with little ICAM-1 expression synthesized DNA actively. ICAM-1 on endothelial cells serves as an anchor for the leukocytes in cell-cell adhesion.(ABSTRACT TRUNCATED AT 250 WORDS)