Polymorphonuclear leukocyte (PMN)–mediated tissue injury.

If the orderly process of PMN transmigration is altered by a stimulus coming from the intravascular space (arrows) rather than the tissues, these intravascular stimuli activate vascular endothelial cells (ECs) and cause attraction, firm adhesion and priming of PMNs. As shown the vascular endothelium is activated causing the release of chemokines (stars) that attract PMNs to the endothelial surface followed by selectin-mediated tethering and firm adhesion through the ICAM-1:β₂-integrin interaction. However, since there are not signals to cause diapedesis and PMN chemotaxis into the tissues, the PMNs become sequestered, and these primed, hyper-reactive leukocytes may be activated by stimuli that normally have no effect including antibodies directed against specific leukocyte antigens or the lipids that accumulate during routine storage of cellular blood components. Activation of these adherent PMNs causes endothelial damage (ECs with diagonal lines), capillary leak (the large arrow), and organ injury.¹⁰