title: Differential effect of surfactant and its saturated phosphatidylcholines on human blood macrophages.
abstract: 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 alphaCD3-induced T cell proliferation. Human macrophages were exposed to surfactant (Curosurf(R)), 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 Lissaminetrade mark-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 alphaCD3-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.
authors.affiliation: University Children's Hospital, Department of Neonatology, Calwerstr. 7, 72076 Tuebingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Gille
authors.forename: Bärbel
authors.initials: B
authors.lastname: Spring
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bernhard
authors.forename: Caroline
authors.initials: C
authors.lastname: Gebhard
authors.forename: Denise
authors.initials: D
authors.lastname: Basile
authors.forename: Kirsten
authors.initials: K
authors.lastname: Lauber
authors.forename: Christian F
authors.initials: CF
authors.lastname: Poets
authors.forename: Thorsten W
authors.initials: TW
authors.lastname: Orlikowsky
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D010641:Phenotype; D010713:Phosphatidylcholines / Q000494:pharmacology*; D011663:Pulmonary Surfactants / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051116:Receptors, Scavenger / Q000378:metabolism; D013379:Substrate Specificity; D013501:Surface-Active Agents / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology
chemical_list: D010713:Phosphatidylcholines; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D051116:Receptors, Scavenger; D013501:Surface-Active Agents