title: SP-A preserves airway homeostasis during Mycoplasma pneumoniae infection in mice.
abstract: The lung is constantly challenged during normal breathing by a myriad of environmental irritants and infectious insults. Pulmonary host defense mechanisms maintain homeostasis between inhibition/clearance of pathogens and regulation of inflammatory responses that could injure the airway epithelium. One component of this defense mechanism, surfactant protein-A (SP-A), exerts multifunctional roles in mediating host responses to inflammatory and infectious agents. SP-A has a bacteriostatic effect on Mycoplasma pneumoniae (Mp), which occurs by binding surface disaturated phosphatidylglycerols. SP-A can also bind the Mp membrane protein, MPN372. In this study, we investigated the role of SP-A during acute phase pulmonary infection with Mp using mice deficient in SP-A. Biologic responses, inflammation, and cellular infiltration, were much greater in Mp infected SP-A(-/-) mice than wild-type mice. Likewise, physiologic responses (airway hyperresponsiveness and lung compliance) to Mp infection were more severely affected in SP-A(-/-) mice. Both Mp-induced biologic and physiologic changes were attenuated by pharmacologic inhibition of TNF-alpha. Our findings demonstrate that SP-A is vital to preserving lung homeostasis and host defense to this clinically relevant strain of Mp by curtailing inflammatory cell recruitment and limiting an overzealous TNF-alpha response.
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: Hisatsugu
authors.initials: H
authors.lastname: Goto
authors.forename: Erin N
authors.initials: EN
authors.lastname: Potts
authors.forename: Simone
authors.initials: S
authors.lastname: Degan
authors.forename: Hong Wei
authors.initials: HW
authors.lastname: Chu
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Voelker
authors.forename: Mary E
authors.initials: ME
authors.lastname: Sunday
authors.forename: George J
authors.initials: GJ
authors.lastname: Cianciolo
authors.forename: William M
authors.initials: WM
authors.lastname: Foster
authors.forename: Monica
authors.initials: M
authors.lastname: Kraft
authors.forename: Jo Rae
authors.initials: JR
authors.lastname: Wright
mesh_terms: D000818:Animals; D018893:Bronchoalveolar Lavage; D006706:Homeostasis / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009177:Mycoplasma pneumoniae / Q000502:physiology*; D011019:Pneumonia, Mycoplasma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D037662:Pulmonary Surfactant-Associated Protein A / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: D037662:Pulmonary Surfactant-Associated Protein A; D014409:Tumor Necrosis Factor-alpha