The two-event model of acute lung injury (ALI).

The stimulus (endotoxin = LPS) for proinflammatory endothelial activation comes from the intravascular space resulting in firm adherence of PMNs through: (1) slowing of vascular flow and L-selectin–mediated loose attachment and P- and E-selectin–induced tethering and (2) chemokine-induced firm adhesion and sequestration of PMNs. These firmly adherent, sequestered PMNs may be activated by a second agonist (3), the infusion of specific antibodies directed against granulocyte antigens or biologic response modifiers resulting in activation of PMNs endothelial damage (4), capillary leak, and ALI (5).

Reprinted with permission from Silliman CC, Kelher M. Transfusion. 2005 (suppl);45:109S-16S.