title: Surfactant protein A is defective in abrogating inflammation in asthma.
abstract: Surfactant protein A (SP-A) regulates a variety of immune cell functions. We determined the ability of SP-A derived from normal and asthmatic subjects to modulate the inflammatory response elicited by Mycoplasma pneumoniae, a pathogen known to exacerbate asthma. Fourteen asthmatic and 10 normal control subjects underwent bronchoscopy with airway brushing and bronchoalveolar lavage (BAL). Total SP-A was extracted from BAL. The ratio of SP-A1 to total SP-A (SP-A1/SP-A) and the binding of total SP-A to M. pneumoniae membranes were determined. Airway epithelial cells from subjects were exposed to either normal or asthmatic SP-A before exposure to M. pneumoniae. IL-8 protein and MUC5AC mRNA were measured. Total BAL SP-A concentration did not differ between groups, but the percentage SP-A1 was significantly increased in BAL of asthmatic compared with normal subjects. SP-A1/SP-A significantly correlated with maximum binding of total SP-A to M. pneumoniae, but only in asthma. SP-A derived from asthmatic subjects did not significantly attenuate IL-8 and MUC5AC in the setting of M. pneumoniae infection compared with SP-A derived from normal subjects. We conclude that SP-A derived from asthmatic subjects does not abrogate inflammation effectively, and this dysfunction may be modulated by SP-A1/SP-A.
authors.affiliation: Department of Medicine and Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Voelker
authors.forename: Njira L
authors.initials: NL
authors.lastname: Lugogo
authors.forename: Guirong
authors.initials: G
authors.lastname: Wang
authors.forename: Joanna
authors.initials: J
authors.lastname: Floros
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Ingram
authors.forename: Hong Wei
authors.initials: HW
authors.lastname: Chu
authors.forename: Tony D
authors.initials: TD
authors.lastname: Church
authors.forename: Pitchaimani
authors.initials: P
authors.lastname: Kandasamy
authors.forename: Daniel
authors.initials: D
authors.lastname: Fertel
authors.forename: Jo Rae
authors.initials: JR
authors.lastname: Wright
authors.forename: Monica
authors.initials: M
authors.lastname: Kraft
mesh_terms: D000328:Adult; D001249:Asthma / Q000150:complications / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D001999:Bronchoscopy; D016022:Case-Control Studies; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology; D016209:Interleukin-8 / Q000096:biosynthesis; D008297:Male; D055271:Mucin 5AC / Q000096:biosynthesis; D009177:Mycoplasma pneumoniae / Q000276:immunology / Q000378:metabolism*; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014162:Transfection
chemical_list: D016209:Interleukin-8; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D037662:Pulmonary Surfactant-Associated Protein A; D012333:RNA, Messenger; D011994:Recombinant Proteins; C445842:SFTPA1 protein, human