26 Phagocytic functions and TNF secretion of huaan aonocytes exposed to natural porcine surfactant (Curosurf)

Abstract

In this study we have analyzed various phagocytic functions and TNF secretion of human monocytes exposed to either biochemically well defined porcine surfactant or a purified phospholipid preparation. Adherence, random migration and chemotactic response to zymosan activated serum and formyl-methionyl-leucyl-phenylalanine was normal in surfactant treated monocytes; surfactant was not a chemotactic stimulus. In contrast, phagocytosis of S. aureus by monocytes exposed to surfactant (100 μg/ml) and phospholipids (100 μg/ml) was slightly impaired (surfactant: t30 48.5 ± 11 %, t60 73.3 ± 10.1 %; phospholipids: t30 47.3 ± 2.5 %, t60 68.0 ± 6.6 %; controls: t30 66.6 ± 9.9 %, t60 81.0 ± 6.6 %, p<0.05 at t30 for both, P<0.05 at t60 for phospholipids. Due to the smaller number of S. aureus ingested, bactericidal activity of surfactant/phospholipid treated monocytes was slightly reduced when compared with controls (surfactant t60 < 0.05, phospholipids t60 < 0.01). Surfactant and phospholipids had no bactericidal activity. Uptake of Candida was identical in surfactant/phospholipid treated monocytes and untreated controls; the same was true with the number of Candida per cell ingested. Phagocytosis-associated chemiluminescence and production of superoxide anion by monocytes of either source in response to phorbol myristate acetate and opsonized zymosan was also identical. Surfactant and phospholipids, however, effectively suppressed TNF secretion by resting and by LPS-stimuteted monocytes in a dose dependent fashion. TNF is an important mediator of inflammation (LPS-stimulated monocytes controls: 3004 ± 570 pg/ml, LPS ? surfactant (500 μg/ml): 426 ± 162, LPS + phospholipids (500 μg/ml>: 28 ± 9.6; p<0.001 for both). These data suggest that surfactant and phospholipids by suppressing monocytes TNF secretion may have an important role in down regulating inflammatory reactions in the lung.