The neutrophil is the principal cellular component of the inflammatory host defense and contributor to host injury after severe physiologic insult. The neutrophil is inherently coupled to patient outcome in both health and disease and extensive research has focused on the mechanisms that regulate neutrophil delivery, function, and clearance from the inflammatory microenvironment.
The neutrophil cell membrane mediates the interaction of the neutrophil with the extracellular environment; it expresses a complex array of adhesion molecules and receptors for various ligands, including mediators, cytokines, immunoglobulins, and membrane molecules on other cells. Studies have shown that a change in neutrophil membrane expression is synonymous with change in neutrophil function in vivo.1-3 Our research has shown that exudate polymorphonuclear neutrophils are confirmed to have delayed apoptosis as a result of the loss of TNF-alpha receptors during transmigration, which is necessary for neutrophil survival in the extravascular inflammatory milieu.2 Furthermore, a change in polymorphonuclear chemoattractant receptor expression serves to regulate PMN (e.g. neutrophil) chemotaxis, where reduced levels of chemoattractant receptors and chemotaxis in PMN’s from septic patients may explain decreased PMN delivery in these patients.1 Employing a complementary analysis of the neutrophil as a complex system, neutrophil membrane expression may be regarded as a measure of neutrophil connectivity, with altered patterns of connectivity representing functionally distinct neutrophil states. Thus, not only does the neutrophil membrane mediate the processes that characterize the neutrophil lifecycle, but characterization of neutrophil membrane expression represents a technology with which to evaluate neutrophil function.
Relevant Papers:
- Seely AJE, Pascual JL, Christou NV. Science review: Cell membrane expression (connectivity) regulates neutrophil delivery, function and clearance. Crit Care. 2003 Aug; 7(4):291-307.
- Seely AJE, Naud JF, Campisi G, Giannias B, Liu S, DiCarlo A, Ferri LE, Pascual JL, Tchervenkov J, Christou NV. Alteration of chemoattractant receptor expression regulates human neutrophil chemotaxis in vivo. Ann Surg. 2002 Apr; 235(4):550-9.
- Seely AJE, Swartz DE, Giannias B, Christou NV. Reduction in neutrophil cell surface expression of tumor necrosis factor receptors but not Fas after transmigration: implications for the regulation of neutrophil apoptosis. Arch Surg. 1998 Dec; 133(12):1305-10.
