Alpha-4 Integrin: A Novel Mechanism for Neutrophil-endothelial Interaction

Abstract

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 [3]. 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 [4]. 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].