Surfactant protein-A and phosphatidylglycerol suppress type IIA phospholipase A2 synthesis via nuclear factor-kappaB.
We previously showed that surfactant inhibits the synthesis of type IIA secretory phospholipase A2 (sPLA2-IIA) by alveolar macrophages. These cells have been identified as the main source of this enzyme in an animal model of acute lung injury. The aim of the present study was to identify the surfactant components involved in the inhibition of sPLA2-IIA expression in alveolar macrophages and the signaling pathways that mediate this inhibition. Our results show that various surfactant preparations can inhibit sPLA2-IIA expression in endotoxin-stimulated alveolar macrophages. Both the surfactant protein (SP)-A and the surfactant phospholipid fraction inhibit this expression. The surfactant phospholipid dioleylphosphatidylglycerol (DOPG) abolishes sPLA2-IIA expression, whereas dipalmitoylphosphatidylcholine does not. Chromatographic analysis and confocal microscopy revealed that phosphatidylglycerol was rapidly incorporated and metabolized by alveolar macrophages and that its metabolites accumulate in the cytosol. Nuclear factor-kappaB (NF-kappaB) modulates sPLA2-IIA expression in endotoxin-activated alveolar macrophages, and surfactant preparations, surfactant phospholipid fraction, SP-A, and DOPG indeed suppressed NF-kappaB activation. In summary, our results show that SP-A and DOPG play a role in the surfactant-mediated inhibition of sPLA2-IIA expression in alveolar macrophages and that this inhibition occurs via a downregulation of NF-kappaB activation.
Wu
Yong-Zheng
YZ
Unité de Défense Innée et Inflammation/INSERM E336, Institut Pasteur, 75015 Paris, France.
Medjane
Samir
S
Chabot
Sophie
S
Kubrusly
Flavia Saldanha
FS
Raw
Isaias
I
Chignard
Michel
M
Touqui
Lhousseine
L
D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D002855:Chromatography, Thin Layer; D015536:Down-Regulation; D006168:Guinea Pigs; D016676:Macrophages, Alveolar / Q000502:physiology; D008297:Male; D018613:Microscopy, Confocal; D023421:Models, Animal; D016328:NF-kappa B / Q000502:physiology*; D010715:Phosphatidylglycerols / Q000494:pharmacology*; D010741:Phospholipases A / Q000096:biosynthesis* / Q000187:drug effects*; D054467:Phospholipases A2; D011336:Probability; D037662:Pulmonary Surfactant-Associated Protein A / Q000494:pharmacology*; D011663:Pulmonary Surfactants / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D012680:Sensitivity and Specificity; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D016328:NF-kappa B; D010715:Phosphatidylglycerols; D037662:Pulmonary Surfactant-Associated Protein A; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D010741:Phospholipases A; D054467:Phospholipases A2