Modified natural porcine surfactant inhibits superoxide anions and proinflammatory mediators released by resting and stimulated human monocytes.
Pulmonary surfactant has a potential role in modulating inflammation in normal and injured lungs. In lung injury, monocytes become activated and participate in lung inflammation. We therefore, investigated the proinflammatory functions of stimulated human blood monocytes after an overnight preincubation period with modified natural porcine surfactant (Curosurf) (500-1000 micrograms/mL). Monocytes were stimulated either with phorbol myristate acetate (PMA), bacterial extract OM-85, lipopolysaccharide (LPS), or Ca2+ ionophore A23187. The present study shows that Curosurf significantly inhibits: 1) the production of superoxide anions stimulated with OM-85 (1 mg/mL, 30 min), but not with PMA (100 ng/mL, 30 min); 2) the release of cyclooxygenase metabolites prostaglandin E2 and thromboxane B2 stimulated with OM-85 (1 mg/mL, overnight); 3) the release of lipoxygenase metabolite leukotriene C4 stimulated with A23187 (10 microM, 10 min); 4) the release of the cytokine TNF-alpha stimulated overnight with either OM-85 (1 mg/mL) or LPS (10 micrograms/mL)) in a dose-dependent fashion. In addition, Curosurf decreases the spontaneous adherence of monocytes to plastic culture wells in a dose-dependent fashion. Experiments performed with staurosporine, an inhibitor of protein kinase C (PKC) indicate that, in contrast with PMA, the production of superoxide anions stimulated by OM-85 is not related to PKC activation. Consequently, we propose that the mechanism involved in the suppressive effects of Curosurf is PKC-independent. In summary, the present study provides experimental evidence that favors the anti-inflammatory role of modified natural porcine surfactant (Curosurf) in human monocytes in vitro.
Walti
H
H
Service de Médecine Néonatale, UFR Cochin-Port Royal, Paris, France.
Polla
B S
BS
Bachelet
M
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001419:Bacteria; D002448:Cell Adhesion / Q000187:drug effects; D002457:Cell Extracts; D002478:Cells, Cultured; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D019311:Staurosporine / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects; D000095983:Bacterial Lysates
D000276:Adjuvants, Immunologic; D016718:Arachidonic Acid; D002457:Cell Extracts; D011663:Pulmonary Surfactants; D019311:Staurosporine; D013481:Superoxides; D014409:Tumor Necrosis Factor-alpha; C030259:Broncho-Vaxom; D000095983:Bacterial Lysates