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.
Highlights
Blood monocyte-derived macrophages invading the alveolus encounter pulmonary surfactant, a phospholipoprotein complex that changes composition during lung development
Statistical analysis was performed using the decadic logarithm of the values of CD14, CD80, CD86, HLA-DR, TLR2, TLR4, HLA-ABC, CD16, green fluorescent protein (GFP), and 5-carboxyfluorescein discetate succinimidyl ester (CSFE) for a Student’s t-test (Sigmaplot 2000 software for Windows; SPSS, Chicago, IL)
PC16:0/16:0 did not influence HLA-DR expression (P 5 0.52 vs. control) or the percentage of CD80-positive macrophages (P 5 0.27 vs. control; Fig. 1D, E), whereas TLR2 and TLR4 expression was upregulated by 130% and 98%, respectively
Summary
Blood monocyte-derived macrophages invading the alveolus encounter pulmonary surfactant, a phospholipoprotein complex that changes composition during lung development. Curosurf and palmitoylmyristoyl-PC inhibited aCD3induced T cell proliferation by 50%, whereas dipalmitoylPC 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.—Gille, C., B. Surfactant composition changes characteristically during development, with increasing concentrations of disaturated PC species such as PC16:0/14:0 and PC16:0/16:0 at the expense of ubiquituous components such as palmitoyloleoyl-PC (PC16:0/18:1) and, a relative preponderance of PC16:0/14:0 in term neonates compared with adult organisms [2, 3]. In addition to its function in reducing surface tension in the terminal air spaces, surfactant is part of the local pulmonary host defense Both innate immune functions, such as induction of respiratory burst, as well as adaptive tasks, are influenced by surfactant (as reviewed in Ref. 5). Alterations in lipid composition caused by interstitial lung diseases, such as sarcoidosis, hypersensitivity pneumonitis, and idiopathic pulmonary fibrosis, led to changes in immunomodulatory properties of surfactants [9, 10]
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