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J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M600451-JLR200 on November 27, 2006 Originally published In Press as doi:10.1194/jlr.M600451-JLR200 on November 10, 2006

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Journal of Lipid Research, Vol. 48, 307-317, February 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Differential effect of surfactant and its saturated phosphatidylcholines on human blood macrophages

Christian Gille*, Bärbel Spring*, Wolfgang Bernhard*, Caroline Gebhard*, Denise Basile*, Kirsten Lauber{dagger}, Christian F. Poets* and Thorsten W. Orlikowsky1,*

* University Children's Hospital, Department of Neonatology, Calwerstr. 7, 72076 Tuebingen, Germany
{dagger} Department of Internal Medicine, Section of Molecular Gastroenterology, Otfried-Mueller-Str. 10, 72076 Tuebingen, Germany

Published, JLR Papers in Press, November 10, 2006.

1 To whom correspondence should be addressed: e-mail: thorsten.orlikowsky{at}med.uni-tuebingen.de

Blood monocyte-derived macrophages invading the alveolus encounter pulmonary surfactant, a phospholipoprotein complex that changes composition during lung development. We tested the hypothesis that characteristic phosphatidylcholine (PC) components differentially influence macrophage phenotype and function, as determined by phagocytosis of green fluorescent protein-labeled Escherichia coli and {alpha}CD3-induced T cell proliferation. Human macrophages were exposed to surfactant (Curosurf®), to two of its characteristic phosphadidylcholine (PC) components (dipalmitoyl-PC and palmitoylmyristoyl-PC), and to a ubiquituous PC (palmitoyloleoyl-PC) as control. Interaction of Curosurf and PC species with macrophages was assessed using LissamineTM-dihexadecanoyl-phosphoethanolamine-labeled liposomes. Curosurf and both saturated surfactant PC species downregulated CD14 expression and upregulated CD206. HLA-DR and CD80 were upregulated by Curosurf and palmitoylmyristoyl-PC, whereas dipalmitoyl-PC showed no effect. The latter upregulated TLR2 and TLR4 expression, whereas Curosurf and palmitoylmyristoyl-PC had no effect. PC species tested were incorporated in comparable amounts by macrophages. Curosurf and PC species inhibited phagocytosis of E. coli. Scavenger receptor CD36, CD68, SR-A, and LOX-1 mRNA expression was upregulated by Curosurf, whereas PC species only upregulated SR-A. Curosurf and palmitoylmyristoyl-PC inhibited {alpha}CD3-induced T cell proliferation by 50%, whereas dipalmitoyl-PC and palmitoyloleoyl-PC showed no effect. These data identify individual surfactant PC species as modifiers of macrophage differentiation and suggest differential effects on innate and adaptive immune functions.

Supplementary key words phospholipids • molecular species • PC16:0/14:0 • PC16:0/16:0 • costimulation • HLA-DR

Abbreviations: CSFE, 5-carboxyfluorescein discetate succinimidyl ester; DAPI, 4',6-diamidino-2-phenylindol; DHPE, 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine; FSC, forward scatter; GFP, green fluorescent protein; MFI, mean fluorescence intensity; PBMNC, peripheral blood mononuclear cell; PC, phosphatdylcholine; PE, phosphatidylethanolamine; PG, phosphatidylglycerol; PI, phosphatidylinositol; SP, surfactant protein; SSC, sideward scatter


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