The FASEB Journal, Vol 8, 504-512, Copyright © 1994 by The Federation of American Societies for Experimental Biology

REVIEWS

Adhesion molecules and inflammatory injury

SM Albelda, CW Smith and PA Ward
Department of Medicine, University of Pennsylvania Medical Center, Philadelphia 19104.

Neutrophil-endothelial cell interactions are mediated by interacting sets of cell adhesion molecules (CAMs) and chemoattractant/activator molecules to form an "adhesion cascade." The initial phase of inflammation, a transient slowing of neutrophils in postcapillary venules, is mediated by selectins. Subsequently, firm adhesion of neutrophils to the vessel wall occurs via interaction of the CD11/CD18 (beta 2) integrins to endothelial ligands such as intercellular adhesion molecule-1 (ICAM-1). This binding requires activation of CD11/CD18 by exposure of the neutrophil to a variety of activating/chemoattractant molecules, such as platelet-activating factor or interleukin-8. Finally, transmigration into tissues occurs, a process that requires both a chemotactic stimulus and engagement of platelet-endothelial cell adhesion molecule-1 (PECAM-1). Several approaches have been used to probe the role of CAMs in vivo. These include the use of blocking antibodies, chimeric selectin- immunoglobulin proteins, sialyl Lewisx oligosaccharides and peptides, along with the study of humans and animals with genetically determined adhesion deficiencies. These studies demonstrate that CAM blockade can effectively inhibit inflammation; however, there appear to be clear differences in the adhesion requirements for particular types of inflammation. By understanding the CAM/chemoattractant profiles involved in specific disease states, it may be possible to precisely and effectively target therapy to a wide variety of inflammatory diseases.

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				H. Kobuchi, S. Roy, C. K. Sen, H. G. Nguyen, and L. Packer Quercetin inhibits inducible ICAM-1 expression in human endothelial cells through the JNK pathway Am J Physiol Cell Physiol, September 1, 1999; 277(3): C403 - C411. [Abstract] [Full Text] [PDF]

				M. Kamochi, F. Kamochi, Y. B. Kim, S. Sawh, J. M. Sanders, I. Sarembock, S. Green, J. S. Young, K. Ley, S. M. Fu, et al. P-selectin and ICAM-1 mediate endotoxin-induced neutrophil recruitment and injury to the lung and liver Am J Physiol Lung Cell Mol Physiol, August 1, 1999; 277(2): L310 - L319. [Abstract] [Full Text] [PDF]

				F. Zeni, C. Parent, R. Correa, C. Natanson, B. Freeman, J. Fontana, M. Quezado, R. L. Danner, Y. Fitz, S. Richmond, et al. ICAM-1 and CD11b inhibition worsen outcome in rats with E. coli pneumonia J Appl Physiol, July 1, 1999; 87(1): 299 - 307. [Abstract] [Full Text] [PDF]

				G. Asimakopoulos Mechanisms of the systemic inflammatory response Perfusion, July 1, 1999; 14(4): 269 - 277. [PDF]

				G. P. Downey, Q. Dong, J. Kruger, S. Dedhar, and V. Cherapanov Regulation of Neutrophil Activation in Acute Lung Injury Chest, July 1, 1999; 116 (2009): 46S - 54S. [Full Text]

				B. Y. Poon, C. A. Ward, W. R. Giles, and P. Kubes Emigrated Neutrophils Regulate Ventricular Contractility via {alpha}4 Integrin Circ. Res., June 11, 1999; 84(11): 1245 - 1251. [Abstract] [Full Text] [PDF]

				P. A. Ward and A. B. Lentsch The Acute Inflammatory Response and Its Regulation Arch Surg, June 1, 1999; 134(6): 666 - 669. [Abstract] [Full Text] [PDF]

				J. Reckless, E. M. Rubin, J. B. Verstuyft, J. C. Metcalfe, and D. J. Grainger Monocyte Chemoattractant Protein-1 but Not Tumor Necrosis Factor-{alpha} Is Correlated With Monocyte Infiltration in Mouse Lipid Lesions Circulation, May 4, 1999; 99(17): 2310 - 2316. [Abstract] [Full Text] [PDF]

				M. Chello, P. Mastroroberto, E. Malta, F. Cirillo, and V. Celi Inhibition by dipyridamole of neutrophil adhesion to vascular endothelium during coronary bypass surgery Ann. Thorac. Surg., May 1, 1999; 67(5): 1277 - 1282. [Abstract] [Full Text] [PDF]

				W. KARZAI, B. U. von SPECHT, C. PARENT, J. HABERSTROH, K. WOLLERSEN, C. NATANSON, S. M. BANKS, and PETER. Q. EICHACKER G-CSF during Escherichia coli versus Staphylococcus aureus Pneumonia in Rats Has Fundamentally Different and Opposite Effects Am. J. Respir. Crit. Care Med., May 1, 1999; 159(5): 1377 - 1382. [Abstract] [Full Text] [PDF]

				J. M. Yanni, L. K. Weimer, N. A. Sharif, S. X. Xu, D. A. Gamache, and J. M. Spellman Inhibition of Histamine-Induced Human Conjunctival Epithelial Cell Responses by Ocular Allergy Drugs Arch Ophthalmol, May 1, 1999; 117(5): 643 - 647. [Abstract] [Full Text] [PDF]

				M. Krull, A. C. Klucken, F. N. Wuppermann, O. Fuhrmann, C. Magerl, J. Seybold, S. Hippenstiel, J. H. Hegemann, C. A. Jantos, and N. Suttorp Signal Transduction Pathways Activated in Endothelial Cells Following Infection with Chlamydia pneumoniae J. Immunol., April 15, 1999; 162(8): 4834 - 4841. [Abstract] [Full Text] [PDF]

				H. Sakurai, F. C. Schmalstieg, L. D. Traber, H. K. Hawkins, and D. L. Traber Role of L-selectin in physiological manifestations after burn and smoke inhalation injury in sheep J Appl Physiol, April 1, 1999; 86(4): 1151 - 1159. [Abstract] [Full Text] [PDF]

				W. M. ABRAHAM, A. AHMED, J. R. SABATER, I. T. LAUREDO, Y. BOTVINNIKOVA, R. J. BJERCKE, X. HU, B. M. REVELLE, T. P. KOGAN, I. L. SCOTT, et al. Selectin Blockade Prevents Antigen-induced Late Bronchial Responses and Airway Hyperresponsiveness in Allergic Sheep Am. J. Respir. Crit. Care Med., April 1, 1999; 159(4): 1205 - 1214. [Abstract] [Full Text] [PDF]

				Q. Dong, K. A. Siminovitch, L. Fialkow, T. Fukushima, and G. P. Downey Negative Regulation of Myeloid Cell Proliferation and Function by the SH2 Domain-Containing Tyrosine Phosphatase-1 J. Immunol., March 15, 1999; 162(6): 3220 - 3230. [Abstract] [Full Text] [PDF]

				S. SALVI, A. BLOMBERG, B. RUDELL, F. KELLY, T. SANDSTRÖM, S. T. HOLGATE, and A. FREW Acute Inflammatory Responses in the Airways and Peripheral Blood After Short-Term Exposure to Diesel Exhaust in Healthy Human Volunteers Am. J. Respir. Crit. Care Med., March 1, 1999; 159(3): 702 - 709. [Abstract] [Full Text]

				A. Mocsai, E. Ligeti, C. A. Lowell, and G. Berton Adhesion-Dependent Degranulation of Neutrophils Requires the Src Family Kinases Fgr and Hck J. Immunol., January 15, 1999; 162(2): 1120 - 1126. [Abstract] [Full Text] [PDF]