Alpha-4 Integrin: A Novel Mechanism for Neutrophil-endothelial Interaction
The systemic inflammatory response syndrome (SIRS) is a ubiquitous characteristic of critically ill, intensive care unit (ICU) patients. The most commonly studied condition that results in SIRS is septic shock. In septic shock, a microbial agent causes a localized tissue injury resulting in a systemic inflammatory response leading to secondary injury to organs not primarily infected by the microbial agent. The consequence of secondary organ injury is often serious morbidity or death from multisystern organ failure (MOF). Severe sepsis syndrome/septic shock continues to be associated with a mortality rate of 20–50% in most tertiary care ICUs [1, 2] Despite advances in the physiologic support of these patients, and multiple studies assessing the activation of the inflammatory cascade and therapeutic interventions with immunomodulatory therapy, consistently effective treatment remains elusive . In fact, the only therapy recently demonstrated to be effective, recombinant human activated protein C, targets the coagulation cascade rather than acting as a specific ‘anti-inflammatory’ agent . Although the inflammatory and coagulation cascades are related, the pathophysiology of the association, including neutrophil activation and endothelial interactions, remains poorly understood. Activation and migration of leukocytes, specifically neutrophils, to sites of primary and secondary tissue injury is the basis of the pathogenesis of inflammatory conditions including septic shock [5-7].
KeywordsSeptic Shock Human Umbilical Vein Endothelial Cell Systemic Inflammatory Response Syndrome Septic Patient Necrotizing Fasciitis
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- 1.Centers for Disease Control and Prevention, National Center for Health Statistics (1993) Mortality pattern - United States 1990. Monthly Vital Stat Rep 41: 5Google Scholar
- 10.Von Andrian U, Hansell P, Chambers J, et al (1992) L-selectin function is required for beta-2-integrin mediated neutrophil adhesion at physiological shear rates in vivo. Am J Physiol 263: H1034 - H1044Google Scholar
- 19.Tonneson M, Anderson D, Springer T, Knelder A, Avdi N, Henson P (1989) Adherence of neutrophils to cultured human microvasculature endothelial cells. Stimulation by chemotactic peptides and lipid mediators and dependence upon the Mac-1, LFA, p150,95 Glycoprotein family. J Clin Invest 83: 637–646CrossRefGoogle Scholar
- 20.Kishimoto T, Anderson D (1992) The role of integrins in inflammation. In: Gallin J, Goldstein I, Snyderman R (eds) Inflammation: Basic Principles and Clinical Correlates. Raven Press, New York, pp 353–406Google Scholar
- 23.Kanwar S, Bullard D, Hickey M, et al (1997) The association between alpha-4 integrin, Pselectin, and E-selectin in an allergic model of inflammation. J Exp Med 185: 1077–1087Google Scholar
- 24.Molossi S, Elices M, Arrhenius T, Diaz R, Coubler C, Rabinovitch M (1995) Blockade of very late antigen-4 integrin binding to fibronectin with connecting segment-1 peptide reduces accelerated coronary arteriopathy in rabbit cardiac allografts. J Clin Invest 95: 26012610Google Scholar
- 37.Shappell S, Toman C, Anderson D. Taylor A, Entman M, Smith C (1990) Mac-1 (CD lib/ CD 18) mediates adherence-dependent hydrogen peroxide production by human and canine neutrophils. J Immunol 144: 2702–2711Google Scholar
- 43.Reinhardt P, Elliott J, Kubes P 11997) Neutrophils can adhere via alpha-4 beta-1 integrin under flow conditions. Blood 89: 3837–3846Google Scholar
- 47.Johnston B, Chee A, Issekutz T (2001) a4 Integrin leukocyte recruitment does not require VCAM-1 in a chronic model of inflammation. J Immunol 164: 3337–3344Google Scholar