Migration of neutrophils from blood to tissue: alteration of modulatory effects of prostanoid on superoxide generation in rabbits and humans.

Alteration of neutrophil function is associated with their migration from blood into tissue. We evaluated this alteration in both human and rabbit neutrophils, by comparing the inhibitory effects of prostanoids on formylmethionyl-leucyl-phenylalanine (fMLP)-stimulated superoxide generation in human circulating blood neutrophils with those in saliva, and also comparing rabbit circulating blood neutrophils with those exudated into peritoneal cavity. We showed that EP-receptor agonists (PGE1) EP2/EP3 agonist (misoprostol), EP2-receptor agonist (butaprost) and DP-receptor agonist (PGD2) inhibited fMLP-stimulated superoxide production from human blood neutrophils in a concentration-dependent manner. In contrast, these prostanoids produced a significantly smaller maximum inhibition of fMLP-stimulated superoxide production in salivary neutrophils compared to those in blood neutrophils. Similar differences were observed for rabbit blood and peritoneal neutrophils. The inhibitory effect of EP2 agonist (butaprost) on the fMLP-stimulated superoxide generation in human blood neutrophils was significantly higher than that of EP3 agonist (ONO-AP-324). The EP1 antagonist (SC-51322) and EP4 antagonist (AH23848B) employed in this study could not antagonize the inhibitory effect of PGE2. TP agonist (U-46619) failed to show any inhibitory effect in either blood or salivary neutrophils. These results indicated that EP2 and DP receptors are the primary receptors mediating the prostanoids inhibition of fMLP-stimulated superoxide generation from neutrophils. Furthermore, it can be concluded that neutrophils become less responsive to prostanoids in terms of fMLP-stimulated superoxide production in association with their migration from blood to tissue.