title: The physiological roles of ICAM-1 and ICAM-2 in neutrophil migration into tissues.
abstract: OBJECTIVE
  Neutrophil 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.
  
  
  RESULTS
  Signalling 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Theodor Kocher Institute, University of Bern, Bern, Switzerland.
authors.forename: Ruth
authors.initials: R
authors.lastname: Lyck
authors.forename: Gaby
authors.initials: G
authors.lastname: Enzmann
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D009504:Neutrophils / Q000166:cytology / Q000502:physiology*; D057705:Transendothelial and Transepithelial Migration / Q000502:physiology*
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C573420:ICAM1 protein, human; C065289:ICAM2 protein, human; D018799:Intercellular Adhesion Molecule-1