The study investigates the interaction between intercellular adhesion molecule (ICAM)-1 and Mac-1 (CD11b/CD18), a related leukocyte integrin. Using multiple cell binding assays, purified Mac-1, and cell lines transfected with Mac-1 and ICAM-1 cDNAs, the authors demonstrate that ICAM-1 binds to Mac-1 in a manner inhibited by mAbs to both Mac-1 and ICAM-1. Transfected murine L cells or monkey COS cells expressing human ICAM-1 bind to purified Mac-1 in a specific and dose-dependent manner, with the attachment being more temperature-sensitive and lower in avidity compared to LFA-1. Reciprocal assays show that COS cells cotransfected with the α and β chain cDNAs of Mac-1 or LFA-1 attach to immunoaffinity-purified ICAM-1 substrates, which is blocked by mAbs to ICAM-1 and Mac-1 or LFA-1. Two-color fluorescence cell conjugate experiments show that neutrophils stimulated with fMLP bind to HUVECs stimulated with lipopolysaccharide for 24 hours in an ICAM-1-, Mac-1-, and LFA-1-dependent fashion. These findings conclude that ICAM-1 is a counter receptor for Mac-1 and that this receptor pair is responsible for the adhesion between stimulated neutrophils and stimulated endothelial cells.The study investigates the interaction between intercellular adhesion molecule (ICAM)-1 and Mac-1 (CD11b/CD18), a related leukocyte integrin. Using multiple cell binding assays, purified Mac-1, and cell lines transfected with Mac-1 and ICAM-1 cDNAs, the authors demonstrate that ICAM-1 binds to Mac-1 in a manner inhibited by mAbs to both Mac-1 and ICAM-1. Transfected murine L cells or monkey COS cells expressing human ICAM-1 bind to purified Mac-1 in a specific and dose-dependent manner, with the attachment being more temperature-sensitive and lower in avidity compared to LFA-1. Reciprocal assays show that COS cells cotransfected with the α and β chain cDNAs of Mac-1 or LFA-1 attach to immunoaffinity-purified ICAM-1 substrates, which is blocked by mAbs to ICAM-1 and Mac-1 or LFA-1. Two-color fluorescence cell conjugate experiments show that neutrophils stimulated with fMLP bind to HUVECs stimulated with lipopolysaccharide for 24 hours in an ICAM-1-, Mac-1-, and LFA-1-dependent fashion. These findings conclude that ICAM-1 is a counter receptor for Mac-1 and that this receptor pair is responsible for the adhesion between stimulated neutrophils and stimulated endothelial cells.