The effect of vasodilator prostaglandins on polymorphonuclear leukocyte infiltration and vascular injury

Some severe acute inflammatory reactions are characterized by polymorphonuclear leukocyte (PMN) infiltration as well as vascular and tissue damage with hemorrhage. Two types of mediators that may be involved in such reactions are chemotactic factors and prostaglandins. The chemotactic factors can induce PMN infiltration, while some types of prostaglandins cause vasodilatation. We reported previously that injection of soluble, nonphagocytosable chemotactic stimuli, zymosan-activated plasma (ZAP), or C5a des Arg into rabbit skin induced PMN-dependent hemorrhage. Here we investigated whether prostaglandins may modulate the rate of PMN infiltration, measured with ⁵¹Cr-labeled leukocytes and the degree of hemorrhage, measured with ⁵⁹Fe-labeled red cells. Prostaglandin (PG) E₁ (0.5 μg) or E₂ (1 μg) increased ZAP-induced PMN accumulation by 81% and hemorrhage by 400%. A similar potentiation by PGE₂ was observed when submaximal concentrations of ZAP were injected. Prostaglandin F₂(α) had no such effect. These results indicate that the degree of PMN infiltration of the tissues may be one factor determining the severity of vascular damage. Furthermore, vasodilatory prostaglandins, generated during neutrophilic inflammatory reactions, may enhance chemotactic-factor-mediated PMN infiltration and increase the extent of vascular injury.