The physiological roles of ICAM-1 and ICAM-2 in neutrophil migration into tissues

Abstract

Purpose of reviewNeutrophil extravasation from the blood into tissues is initiated by tethering and rolling of neutrophils on endothelial cells, followed by neutrophil integrin activation and shear resistant arrest, crawling, diapedesis and breaching the endothelial basement membrane harbouring pericytes. Endothelial intercellular cell adhesion molecule (ICAM)-1 and ICAM-2, in conjunction with ICAM-1 on pericytes, critically contribute to each step. In addition, epithelial ICAM-1 is involved in neutrophil migration to peri-epithelial sites. The most recent findings on the role of ICAM-1 and ICAM-2 for neutrophil migration into tissues will be reviewed here. Recent findingsSignalling via endothelial ICAM-1 and ICAM-2 contributes to stiffness of the endothelial cells at sites of chronic inflammation and junctional maturation, respectively. Endothelial ICAM-2 contributes to neutrophil crawling and initiation of paracellular diapedesis, which then proceeds independent of ICAM-2. Substantial transcellular neutrophil diapedesis across the blood-brain barrier is strictly dependent on endothelial ICAM-1 and ICAM-2. Endothelial ICAM-1 or ICAM-2 is involved in neutrophil-mediated plasma leakage. ICAM-1 on pericytes assists the final step of neutrophil extravasation. Epithelial ICAM-1 rather indirectly promotes neutrophil migration to peri-epithelial sites.Summary ICAM-1 and ICAM-2 are involved in each step of neutrophil extravasation, and have redundant but also distinct functions. Analysis of the role of endothelial ICAM-1 requires simultaneous consideration of ICAM-2.

Pericytes in Brain Injury and Repair After Ischemic Stroke

“…Accumulating evidences confirm the critical role of pericytes in regulating leukocyte adhesion and migration. Pericytes express ICAM-1, which interacts with its intergrin ligands on leukocytes and thus guide leukocyte migration through gaps between adjacent pericytes during ischemia [62–63]. Pericytes at the venular end of capillary beds show a prominent role in regulating neutrophils infiltration.…”

Beyond muscles: The untapped potential of creatine

“…As the levels of creatine increased, the levels of ICAM-1 and E-selectin decreased to control levels at a concentration of 5 mM creatine [17]. In addition to altered surface molecule expression, the study also found that there was a decrease in endothelial permeability and the adhesion of neutrophils to the endothelial cells [17], suggesting that neutrophil extravasation may be affected by creatine use, as adhesion is a key step in this process [230]. These findings would suggest that the immune response may be dampened in the presence of high levels of creatine, despite the presence of pro-inflammatory processes (that is, the production of TNF-α).…”

Cell-stiffness-induced mechanosignaling – a key driver of leukocyte transendothelial migration

“…A structural look at ICAM1 Endothelial ICAM1 is a mechanosensitive adhesion receptor involved in leukocyte TEM. Human ICAM1 contains five extracellular glycosylated Iglike domains (482 residues), a transmembrane domain (22 residues) and a short cytoplasmic region (28 residues) without any binding motif (Lyck and Enzmann, 2015). ICAM1 forms a homodimer through the first and the fourth extracellular Ig-domain.…”

“…Leukocyte binding induces clustering of ICAM1 and VCAM1, which leads to the formation of higher-order clusters and nanodomains, thereby forming adhesive platforms and membrane protrusions that surround adherent leukocytes and support TEM (Barreiro et al, 2002;Carman and Springer, 2004;Phillipson et al, 2008;van Buul et al, 2007). Endothelial ICAM1 plays a central role in leukocyte extravasation because it is involved in leukocyte adhesion, crawling and TEM through the cell body (transcellular TEM) or junctions ( paracellular TEM) (Heemskerk et al, 2014;Lyck and Enzmann, 2015;Nourshargh et al, 2010). ICAM1 consists of five extracellular domains, a transmembrane domain and a short cytoplasmic region (Box 2).…”