Leukocyte-endothelial cell interactions: Molecular mechanisms and implications in gastrointestinal disease  Julián panés*, D.Neil Granger‡  Gastroenterology  Volume 114, Issue 5, Pages 1066-1090 (May 1998) DOI: 10.1016/S0016-5085(98)70328-2 Copyright © 1998 American Gastroenterological Association Terms and Conditions

Fig. 1 Schematic of the multistep model of leukocyte-endothelial cell adhesion. The leukocyte and endothelial cell receptors that contribute to the different steps (rolling, firm adhesion, emigration) in the recruitment cascade are also illustrated. Gastroenterology 1998 114, 1066-1090DOI: (10.1016/S0016-5085(98)70328-2) Copyright © 1998 American Gastroenterological Association Terms and Conditions

Fig. 2 (A) Molecular structure of selectin molecules. All selectins contain a lectin domain, an epidermal growth factor (EGF)-like domain, and several complement binding domains. (B) Molecular structure of adhesion glycoproteins belonging to the immunoglobulin superfamily. The cytoplasmic domain (C terminus region) is indicated as COOH and the protein-bound sugar side chains are represented by circles. C2 stands for constant Ig domain 2, and A1 for an IgA domain. Disulfide bridges are indicated with an S-S. Modified and reprinted with permission.95 Gastroenterology 1998 114, 1066-1090DOI: (10.1016/S0016-5085(98)70328-2) Copyright © 1998 American Gastroenterological Association Terms and Conditions

Fig. 2 (A) Molecular structure of selectin molecules. All selectins contain a lectin domain, an epidermal growth factor (EGF)-like domain, and several complement binding domains. (B) Molecular structure of adhesion glycoproteins belonging to the immunoglobulin superfamily. The cytoplasmic domain (C terminus region) is indicated as COOH and the protein-bound sugar side chains are represented by circles. C2 stands for constant Ig domain 2, and A1 for an IgA domain. Disulfide bridges are indicated with an S-S. Modified and reprinted with permission.95 Gastroenterology 1998 114, 1066-1090DOI: (10.1016/S0016-5085(98)70328-2) Copyright © 1998 American Gastroenterological Association Terms and Conditions

Fig. 3 Kinetics of expression of endothelial cell adhesion molecules in the cytokine (or endotoxin) challenged murine small intestine. The rapid, short-lived expression of P-selectin was induced by engagement of histamine with H1 receptors on endothelial cells. (A) The more prolonged elevation in P-selectin and E-selectin was elicited by endotoxin. (B) ICAM-1, VCAM-1, and PECAM-1 expression was induced by TNF-α. Data from Eppihimer et al.23 and Henninger et al.77 Gastroenterology 1998 114, 1066-1090DOI: (10.1016/S0016-5085(98)70328-2) Copyright © 1998 American Gastroenterological Association Terms and Conditions

Fig. 3 Kinetics of expression of endothelial cell adhesion molecules in the cytokine (or endotoxin) challenged murine small intestine. The rapid, short-lived expression of P-selectin was induced by engagement of histamine with H1 receptors on endothelial cells. (A) The more prolonged elevation in P-selectin and E-selectin was elicited by endotoxin. (B) ICAM-1, VCAM-1, and PECAM-1 expression was induced by TNF-α. Data from Eppihimer et al.23 and Henninger et al.77 Gastroenterology 1998 114, 1066-1090DOI: (10.1016/S0016-5085(98)70328-2) Copyright © 1998 American Gastroenterological Association Terms and Conditions

Fig. 4 Activation of NF-κB via phosphorylation, ubiquination, and proteosome-mediated degradation of I-κB, resulting in increased endothelial cell adhesion molecule synthesis and surface expression. Gastroenterology 1998 114, 1066-1090DOI: (10.1016/S0016-5085(98)70328-2) Copyright © 1998 American Gastroenterological Association Terms and Conditions

Fig. 5 Mechanism proposed to explain the leukocyte-endothelial cell adhesion elicited by I/R. Gastroenterology 1998 114, 1066-1090DOI: (10.1016/S0016-5085(98)70328-2) Copyright © 1998 American Gastroenterological Association Terms and Conditions

Fig. 6 Proposed chain of events that explains the leukocyte-endothelial cell adhesion and tissue damage caused by γ-radiation. Reprinted with permission.236 Gastroenterology 1998 114, 1066-1090DOI: (10.1016/S0016-5085(98)70328-2) Copyright © 1998 American Gastroenterological Association Terms and Conditions

Fig. 7 Mechanism proposed to explain the leukocyte recruitment and increased vascular permeability elicited by C. difficile toxin A. Gastroenterology 1998 114, 1066-1090DOI: (10.1016/S0016-5085(98)70328-2) Copyright © 1998 American Gastroenterological Association Terms and Conditions