ICAM-1 (CD54): a counter-receptor for Mac-1 (CD11b/CD18).

Abstract

Abstract. While the leukocyte integrin lymphocyte function-associated antigen (LFA)-I has been demonstrated to bind intercellular adhesion molecule (ICAM)-I, results with the related Mac-1 molecule have been controversial. We have used multiple cell binding assays, purified Mac-1 and ICAM-1, and cell lines transfected with Mac-1 and ICAM-1 cDNAs to examine the interaction of ICAM-1 with Mac-1. Stimulated human umbilical vein endothelial cells (HUVECs), which express a high surface density of ICAM-1, bind to immunoaffinity-purified Mac-1 adsorbed to artificial substrates in a manner that is inhibited by mAbs to 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; the attachment to Mac-1 is more temperature sensitive, lower in avidity, and blocked by a different series of ICAM-1 mAbs when compared to LFA-1. In a reciprocal assay, COS cells cotransfected with the o~ and/3 chain cDNAs of Mac-1 or LFA-1 attach to immunoaffinity-purified ICAM-1 substrates; this adhesion 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 HUVEC stimulated with lipopolysaccharide for 24 h in an ICAM-I-, Mac-l-, and LFA-l-dependent fashion. Because cellular and purified Mac-1 interact with cellular and purified ICAM-1, we conclude that ICAM-1 is a counter receptor for Mac-1 and that this receptor pair is responsible, in part, for the adhesion between stimulated neutrophils and stimulated endothelial cells.Primary event in the immune system's response to infectious agents is the recruitment of circulating neutrophils to the inflammatory site. Adhesion to the endothelium is the prerequisite physical step for extravasation to the peripheral site of injury. Neutrophil localization has been examined on a molecular level to define both the sequence of events that promotes neutrophil exit from the bloodstream and the cognate proteins on the surface of neutrophils and the endothelial cells that coordinate this interaction.The CDll/CDI8 family defines three high molecular weight, cell surface heterodimeric glycoproteins that have a broad distribution on leukocytes (53). This family, known as the leukocyte integrins, consists of lymphocyte functionassociated antigen (LFA)1-1 (CDlla/CD18; ot 175,000 Mr), Macq (CDllb/CD18; ct 160,000 Mr), and p150,95 (CDllc/ CD18; ot 150,000 Mr); the three proteins share a common 13 (CD18) chain (95,000 Mr) that is noncovalently associated with each unique a chain. These proteins are critical for adhesive functions in the immune system (29): mAbs to LFA-I block leukocyte adhesion to endothelial cells (16,56) 1. Abbt~oviations used in this paper: fMLR formyl methionine-leucinephenylalanine; HE, hydroethidine; HSA, human serum albumin; HUVEC, human umbilical vein endothelial cell; ICAM, intercellular adhesion molecule; IL, interleukin; LFA, lymphocyte function-associated antigen; SFDA, sulfofluorescein &acetate; TEA, trieth...

Neutrophil transepithelial migration: role of toll-like receptors in mucosal inflammation

“…Interestingly, PMN interactions with epithelial JAM-C occur at points distal to initial adhesive interactions with the epithelial basolateral membrane, thus lending further support for the existence of multiple epithelial ligands for migrating PMNs. In closing this section, it is important to note that other adhesion molecules such as ICAM-1 for example, have been reported to bind CD11b/CD18 (Diamond et al 1990) However, ICAM-1 is only expressed on apical epithelial surfaces under inflammatory conditions, which makes ICAM-1 inaccessible to PMNs until after reaching the lumenal surface (Parkos 1997). …”

Serum levels of soluble intercellular adhesion molecule-1 (ICAM-1, CD54) in patients with non-small-cell lung cancer: correlation with histological expression of ICAM-1 and tumour stage

“…ICAM-1 belongs to the immunoglobulin gene superfamily and is the ligand for the P2-integrins, LFA-1 (leucocyte functionassociated antigen-1, CDlla/CD18) and Mac-I (CDllb/CD18) (Diamond et al, 1990;Carlos and Harlan, 1994). The expression of ICAM-1 on the cell surface can be induced by several cytokines (e.g.…”

The integrin αMβ2 anchors hematopoietic progenitors in the bone marrow during enforced mobilization

“…8,9 ␣M␤2 displays highly promiscuous interactions with cellular and extracellular matrix ligands such as intercellular adhesion molecule-1 (ICAM-1) and -2, fibrinogen, iC3b, elastase, sulfated carbohydrates, zymosan, urokinase plasminogen activator, and ␤-glucan. [10][11][12][13][14][15][16][17] In the context of transendothelial migration, ␣M␤2 binds ICAM-1 expressed on activated endothelium and mediates the arrest and diapedesis of leukocytes. 18 Like most other integrins, the affinity of ␣M␤2 for ligands dramatically increases after activation by various stimuli, and its avidity is increased by the translocation to the cell surface of granular stores, a process that parallels the shedding of L-selectin from the surface of neutrophils.…”