| In a normal inflammatory response, the polymorphonuclear neutrophil (PMN) is recruited to a site of injury or infection through a sequence of events that include margination, rolling, adhesion, diapedesis and chemotaxis. These processes become dysregulated in SIRS, sepsis and MODS. Septic patients demonstrate decreased PMN exudation to peripheral sites and an absence of a C5a chemotactic gradient across the intravascular and extravascular environments. Using both in vitro and in vivo PMN transmigration assays, we evaluated the role of an intact C5a gradient on human PMN recruitment to peripheral inflammatory sites in sepsis. We demonstrated in vitro that a C5a gradient could induce both beta2-integrin dependent and independent transendothelial migration of septic PMN. In vivo, the exogenous re-establishment of the C5a gradient increased septic PMN exudation to normal baseline levels. These observations implicate an intact C5a gradient as an essential component to optimal PMN recruitment in sepsis. |
