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(American Journal of Pathology. 2001;159:345-357.)
© 2001 American Society for Investigative Pathology

Regular Articles

PGF₂, a Prostanoid Released by Endothelial Cells Activated by Hypoxia, Is a Chemoattractant Candidate for Neutrophil Recruitment

From the Laboratory of Biochemistry and Cellular Biology, University of Namur, Namur, Belgium

Despite increasing evidence supporting the involvement of neutrophils in ischemic and postischemic damages, the mechanisms underlying the early recruitment of these cells are not completely understood. In this report, the effects of conditioned media from hypoxic endothelial cells on neutrophil chemotaxis were investigated by biochemical and morphological studies. We showed that conditioned media collected from several endothelial cell origins submitted to hypoxia as well as ischemic rat liver perfusion liquids have a chemotactic activity for neutrophils. The role of various chemoattractant molecules like HETEs, platelet-activating factor, and cytokines such as interleukin-8 and interleukin-1 was examined in the same model. Chemotactic peptide contribution was ruled out as boiled conditioned media still trigger chemotaxis. However, cell treatment with cyclooxygenase inhibitors, neutralization of PGF₂ biological activity with polyclonal antibodies, and the neutrophil preincubation with a specific PGF₂ antagonist, all dramatically inhibited neutrophil chemotaxis. A strong chemoattractant effect of pure exogenous PGF₂ or of a synthetic analog was also observed. The major effect of PGF₂ on neutrophil chemotaxis was confirmed ex vivo in a rat liver perfusion ischemic model. These results suggest that PGF₂, a prostanoid abundantly released by the endothelium of hypoxic or ischemic tissues, is a chemoattractant molecule that might be involved in the early recruitment of neutrophils in ischemic organs.

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