IN-VITRO MODULATION OF INDUCED NEUTROPHIL ACTIVATION BY DIFFERENT SURFACTANT PREPARATIONS

Endotracheal surfactant administration has gained an important role in the treatment of respiratory failure, Polymorphonuclear neutrophil gr anulocyte (PMN) activation mediated by chemoattractants, such as inter leukin-8 (IL-8), neutrophil-activating peptide-2 (NAP-2) and formylate d bacterial oligopeptides, has been found to be involved in the pathop hysiology of acute respiratory failure. We investigated potential modu lating effects of commercial surfactant preparations (Exosurf(R), Alve ofact(R), Curosurf(R) and Survanta(R)) on spontaneous and chemoattract ant-induced PMN function, Isolated cytochalasin B (CytB)-treated PMNs from healthy adults were incubated with increasing concentrations of s urfactant. The response of the cells was measured in terms of elastase release from the lysosomes within 30 min. The PMNs showed no direct a ctivation by any of the surfactants tested, However, when cells were s timulated with suboptimal dosages of chemokines, such as IL-8 (2 nM) o r NAP-2 (100 nM), or formyl-methionyl-leucyl-phenylalanine (fMLP) (50 nM), and co-incubated with increasing concentrations of surfactant (0. 05-8 mg . mL(-1)) the release of elastase was markedly modulated depen ding on the surfactant preparation used, Whilst Exosurf(R) and Alveofa ct(R) showed only modest effects on the elastase release induced by al l three mediators, Curosurf(R) and Survanta(R) markedly inhibited the cellular response in a dose-dependent manner, At concentrations above 1 mg . mL(-1), Curosur(R) and Survanta(R) decreased the IL-8, NAP-2 an d fMLP-induced elastase release by 83, 67 and 90%, and by 82, 75 and 8 0%, respectively. In conclusion, exogenous surfactant may modulate the inflammatory response of the airways by affecting the chemoattractant -induced polymorphonuclear neutrophil activation, Surfactant preparati ons with inhibiting properties on neutrophil activation may participat e in the prevention of neutrophil-induced lung damage.