A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1.

TLDR

LFA‑1–mediated homotypic adhesion of phorbol ester‑stimulated lymphocytes requires Mg²⁺ and does not involve LFA‑1 homodimerization, implying a second, distinct adhesion molecule also participates. The study aimed to identify this putative second adhesion molecule. A monoclonal antibody that blocks phorbol ester‑stimulated aggregation of LFA‑1⁺ EBV‑transformed lymphoblasts identified a novel 90‑kDa cell surface protein, ICAM‑1, which is distinct from LFA‑1 in distribution and structure and mediates adhesion in most but not all LFA‑1–dependent reactions.

Abstract

Homotypic adhesion by phorbol ester-stimulated lymphocytes requires LFA-1 and Mg+2 and does not involve like-like interactions between LFA-1 molecules on adjacent cells. The latter finding suggested that a second molecule, distinct from LFA-1, also participates in LFA-1-dependent adhesion. The identification of such a molecule was the object of this investigation. After immunization with LFA-1-deficient EBV-transformed lymphoblastoid cells, a MAb was obtained that inhibits phorbol ester-stimulated aggregation of LFA-1+ EBV lines. This MAb defines a novel cell surface molecule, which is designated intercellular adhesion molecule 1 (ICAM-1). ICAM-1 is distinct from LFA-1 in both cell distribution and structure. In SDS-PAGE, ICAM-1 isolated from JY cells is a single chain of Mr = 90,000. As shown by MAb inhibition, ICAM-1 participates in phorbol ester-stimulated adhesion reactions of B lymphocyte and myeloid cell lines and T lymphocyte blasts. However, aggregation of one T lymphocyte cell line (SKW-3) was inhibited by LFA-1 but not ICAM-1 MAb. It is proposed that ICAM-1 may be a ligand in many, but not all, LFA-1-dependent adhesion reactions.