title: Surfactant protein-A inhibits mycoplasma-induced dendritic cell maturation through regulation of HMGB-1 cytokine activity.
abstract: During pulmonary infections, a careful balance between activation of protective host defense mechanisms and potentially injurious inflammatory processes must be maintained. Surfactant protein A (SP-A) is an immune modulator that increases pathogen uptake and clearance by phagocytes while minimizing lung inflammation by limiting dendritic cell (DC) and T cell activation. Recent publications have shown that SP-A binds to and is bacteriostatic for Mycoplasma pneumoniae in vitro. In vivo, SP-A aids in maintenance of airway homeostasis during M. pneumoniae pulmonary infection by preventing an overzealous proinflammatory response mediated by TNF-α. Although SP-A was shown to inhibit maturation of DCs in vitro, the consequence of DC/SP-A interactions in vivo has not been elucidated. In this article, we show that the absence of SP-A during M. pneumoniae infection leads to increased numbers of mature DCs in the lung and draining lymph nodes during the acute phase of infection and, consequently, increased numbers of activated T and B cells during the course of infection. The findings that glycyrrhizin, a specific inhibitor of extracellular high-mobility group box-1 (HMGB-1) abrogated this effect and that SP-A inhibits HMGB-1 release from immune cells suggest that SP-A inhibits M. pneumoniae-induced DC maturation by regulating HMGB-1 cytokine activity.
authors.affiliation: Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Julie G
authors.initials: JG
authors.lastname: Ledford
authors.forename: Bernice
authors.initials: B
authors.lastname: Lo
authors.forename: Michele M
authors.initials: MM
authors.lastname: Kislan
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Thomas
authors.forename: Katherine
authors.initials: K
authors.lastname: Evans
authors.forename: Derek W
authors.initials: DW
authors.lastname: Cain
authors.forename: Monica
authors.initials: M
authors.lastname: Kraft
authors.forename: Kristi L
authors.initials: KL
authors.lastname: Williams
authors.forename: Jo Rae
authors.initials: JR
authors.lastname: Wright
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D024243:HMGB1 Protein / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009175:Mycoplasma Infections / Q000276:immunology* / Q000378:metabolism; D009177:Mycoplasma pneumoniae / Q000276:immunology; D037662:Pulmonary Surfactant-Associated Protein A / Q000276:immunology* / Q000378:metabolism
chemical_list: D024243:HMGB1 Protein; D037662:Pulmonary Surfactant-Associated Protein A
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