PGE1 inhibits neutrophil adherence and neutrophil-mediated injury to cultured endothelial cells.

Abstract

Prostaglandin E1 (PGE1) has been shown to inhibit acute inflammatory reactions involving vascular permeability changes and subsequent tissue damage caused by immune complex deposition and other inflammatory mediators. These effects have been postulated to be due to functional changes induced in circulating neutrophils by PGE1. We evaluated the ability of PGE1 (1 to 100 microM) to protect endothelial cells (EC) from neutrophil injury induced by C5a or phorbol myristate acetate (PMA). The injury to endothelial monolayers was quantitated by 51Cr loss after an 18-h incubation. In the presence of PGE1, there was a concentration-dependent inhibition of C5a- or PMA-stimulated human neutrophil injury to EC. The protective effect was more effective by pretreatment of neutrophils than EC. Since neutrophil adherence to endothelial cells is thought to be an early event in the sequence resulting in injury to vascular endothelium, we next evaluated the effect of PGE1 on neutrophil adherence to plastic surfaces and EC. In a similar fashion, there was a concentration-dependent inhibition of neutrophil adherence to plastic and EC following stimulation with PMA (10 ng/ml), human C5a (5 micrograms/ml) or formyl-met-leu-phe (FMLP, 2 x 10(-7) M). To investigate a possible mechanism of inhibition of neutrophil adherence to plastic surfaces or EC, expression of the neutrophil surface protein Mo1, previously shown to be associated with increased granulocyte adherence, was measured by fluorescence flow cytometry. Although basal levels of Mo1 expression by unstimulated neutrophils were diminished by PGE1 treatment, there was no significant inhibition of PMA- or FMLP-stimulated Mo1 expression in PGE1-treated neutrophils compared with neutrophils stimulated in the absence of PGE1.(ABSTRACT TRUNCATED AT 250 WORDS)