title: Surfactant protein A down-regulates proinflammatory cytokine production evoked by Candida albicans in human alveolar macrophages and monocytes.
abstract: Surfactant protein A (SP-A) has been implicated in the regulation of pulmonary host defense and inflammatory events. We analyzed the impact of SP-A on the Candida albicans-induced cytokine response in human alveolar macrophages (AM) and its precursor cells, the monocytes, which rapidly expand the alveolar mononuclear phagocyte pool under inflammatory conditions. Both recombinant human SP-A and natural canine SP-A were employed. SP-A dose-dependently down-regulated the proinflammatory cytokine response of AM and monocytes to both viable and nonviable Candida, including TNF-alpha, IL-1beta, macrophage inflammatory protein-1alpha, and monocyte chemoattractant protein-1. In contrast, SP-A did not affect the baseline liberation of these cytokines. The release of the antiinflammatory cytokines IL-1 receptor antagonist and IL-6 was not inhibited by SP-A under baseline conditions and in response to fungal challenge. The inhibitory effect of SP-A on proinflammatory cytokine release was retained upon reassembly of the apoprotein with natural surfactant lipids and in the presence of serum constituents, for mimicry of plasma leakage into the alveolar space. It was not reproduced by the homologous proteins complement component C1q and type IV collagen. It was independent of Candida-SP-A binding and phagocyte C1q receptor occupancy, but apparently demanded SP-A internalization by the mononuclear phagocytes, effecting down-regulation of proinflammatory cytokine synthesis at the transcriptional level. We conclude that SP-A limits excessive proinflammatory cytokine release in AM and monocytes confronted with fungal challenge in the alveolar compartment. These data lend further credit to an important physiological role of SP-A in regulating alveolar host defense and inflammation.
authors.affiliation: Department of Internal Medicine, Justus-Liebig-University, Giessen, Germany. simone.rosseau@innere.med.uni-giessen.de
authors.forename: S
authors.initials: S
authors.lastname: Rosseau
authors.forename: P
authors.initials: P
authors.lastname: Hammerl
authors.forename: U
authors.initials: U
authors.lastname: Maus
authors.forename: A
authors.initials: A
authors.lastname: Günther
authors.forename: W
authors.initials: W
authors.lastname: Seeger
authors.forename: F
authors.initials: F
authors.lastname: Grimminger
authors.forename: J
authors.initials: J
authors.lastname: Lohmeyer
mesh_terms: D001798:Blood Proteins / Q000378:metabolism; D002176:Candida albicans / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology; D018932:Chemokine CCL2 / Q000096:biosynthesis; D054407:Chemokine CCL4; D003094:Collagen / Q000276:immunology; D015922:Complement C1q / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D015536:Down-Regulation / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007375:Interleukin-1 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D009000:Monocytes / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D009844:Oligosaccharides / Q000276:immunology; D011510:Proteolipids / Q000276:immunology*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D001798:Blood Proteins; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D016207:Cytokines; D007375:Interleukin-1; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D009844:Oligosaccharides; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D014409:Tumor Necrosis Factor-alpha; D015922:Complement C1q; D003094:Collagen