CLONING AND COMPARATIVE SEQUENCE-ANALYSIS OF THE GENE ENCODING CANINEINTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1)

Canine intercellular adhesion molecule-1 (ICAM-1) plays a primary role in the adherence of canine neutrophils to endothelial cells and in th e cytotoxicity of canine neutrophils for adult cardiac myocytes, We ha ve cloned the canine ICAM-1 gene and have analyzed the conservation of ICAM-1 amino acid (aa) sequences in man, chimpanzee, mouse, rat and d og, Canine ICAM-1 displays 61% identity with human ICAM-1. Cys residue s critical to the immunoglobulin (Ig) fold structure and four sites of N-linked glycosylation are absolutely conserved in ICAM-1 from all sp ecies. Residues in the cytoplasmic tail associated with cytoskeletal c t-actinin binding are highly conserved, supporting the hypothesis that intracellular attachment is indeed important for ICAM-1 function. Res idues critical for human ICAM-1 binding to the beta(2)-integrin leukoc yte-function-associated antigen 1 (LFA-1) are highly conserved between all species, whereas those residues demonstrated to play an important role in interaction of human ICAM-1 with macrophage activation comple x 1 (Mac-1) are not highly conserved. Residues critical for ICAM-1 bin ding to rhinovirus and malaria-infected red blood cells (IRBC) are not highly conserved.