PGF(2 alpha), a prostanoid released by endothelial cells activated by hypoxia, is a chemoattractant candidate for neutrophil recruitment

Despite increasing evidence supporting the involvement of neutrophils in is chemic and postischemic damages, the mechanisms underlying the early recrui tment of these cells are not completely understood. In this report, the eff ects of conditioned media from hypoxic endothelial cells on neutrophil chem otaxis were investigated by biochemical and morphological studies. We showe d that conditioned media collected from several endothelial cell origins su bmitted to hypoxia as well as ischemic rat liver perfusion liquids have a c hemotactic activity for neutrophils. The role of various chemoattractant mo lecules like HETEs, platelet-activating factor, and cytokines such as inter leukin-8 and interleukin-1 was examined in the same model. Chemotactic pept ide contribution was ruled out as boiled conditioned media still trigger ch emotaxis, However, cell treatment with cyclooxygenase inhibitors, neutraliz ation of PGF(2 alpha) biological activity with polyclonal antibodies, and t he neutrophil preincubation with a specific PGF(2 alpha) antagonist, all dr amatically inhibited neutrophil chemotaxis. A strong chemoattractant effect of pure exogenous PGF(2 alpha) or of a synthetic analog was also observed. The major effect of PGF(2 alpha) on neutrophil chemotaxis was confirmed ex vivo in a rat liver perfusion ischemic model. These results suggest that P GF(2 alpha), a prostanoid abundantly released by the endotheliun of hypoxic or ischemic tissues, is a chemoattractant molecule that might be involved in the early recruitment of neutrophils in ischemic organs.