PHAGOCYTIC FUNCTIONS AND TUMOR-NECROSIS-FACTOR SECRETION OF HUMAN MONOCYTES EXPOSED TO NATURAL PORCINE SURFACTANT (CUROSURF)

In this study we have analyzed various phagocytic functions and tumor necrosis factor (TNF) secretion of human monocytes exposed to either a 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 were normal in surfactant-treated monocytes; surfactant was not a chemotactic stimulus. In contrast, phagocytosis of Staphylococcus aureus by monocytes exposed to surfactant (100-mu-g/mL) or phospholipids (100-mu-g/mL) was slightly impaired [surfactant: at 30 min (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- or phospholipid-treated monocytes was slightly reduced when compared with controls. Surfactant or phospholipids had no bactericidal activity. Uptake of Candida albicans was identical in surfactant- or phospholipid-treated monocytes and untreated controls; the same was true for the number of Candida organisms ingested per cell. Phagocytosis-associated chemiluminescence and production of superoxide anion by monocytes of either source in response to phorbol myristate acetate and opsonized zymosan were also unaffected. Surfactant or phospholipids (500-mu-g/mL), however, effectively suppressed TNF secretion by resting and by lipopolysaccharide (LPS)-stimulated monocytes in a dose-dependent fashion, (LPS-stimulated monocyte controls: 3004 +/- 570 pg/mL; LPS + surfactant: 426 +/- 162 pg/mL; LPS + phospholipids: 28 +/- 9.6 pg/mL; p < 0.001 for both). TNF is an important mediator of inflammation, and our data suggest that surfactant or phospholipids, by suppressing monocyte TNF secretion, may have an important role in down-regulating inflammatory reactions in the lung.