Degradation of pulmonary surfactant protein D by Pseudomonas aeruginosa elastase abrogates innate immune function

被引:96
作者
Alcorn, JF [1 ]
Wright, JR [1 ]
机构
[1] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA
关键词
D O I
10.1074/jbc.M400796200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The alveolar epithelium is lined by surfactant, a lipoprotein complex that both reduces surface tension and mediates several innate immune functions including bacterial aggregation, alteration of alveolar macrophage function, and regulation of bacterial clearance. Surfactant protein-D (SP-D) participates in several of these immune functions, and specifically it enhances the clearance of the pulmonary pathogen Pseudomonas aeruginosa, a common cause of morbidity and mortality in cystic fibrosis (CF) patients. P. aeruginosa secretes a variety of virulence factors including elastase, a zinc-metalloprotease, which degrades both SP-A and SP-D. Here we show that SP-D is cleaved by elastase to produce a stable 35-kDa fragment in a time-, temperature-, and dose-dependent manner. Degradation is inhibited by divalent metal cations, a metal chelator, and the elastase inhibitor, phosphoramidon. Sequencing the SP-D degradation products localized the major cleavage sites to the C-terminal lectin domain. The SP-D fragment fails to bind or aggregate bacteria that are aggregated by intact SP-D. SP-D fragment is observed when normal rat bronchoalveolar lavage (BAL) is treated with Pseudomonas aeruginosa elastase, and SP-D fragments are present in the BAL of CF lung allograft patients. These data show that degradation of SP-D occurs in the BAL environment and that degradation eliminates many normal immune functions of SP-D.
引用
收藏
页码:30871 / 30879
页数:9
相关论文
共 48 条
  • [1] Azghani AO, 2000, LUNG, V178, P181
  • [2] BRUCE MC, 1985, AM REV RESPIR DIS, V132, P529
  • [3] LasA, alkaline protease and elastase in clinical strains of Pseudomonas aeruginosa: Quantification by immunochemical methods
    Coin, D
    Louis, D
    Bernillon, J
    Guinand, M
    Wallach, J
    [J]. FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY, 1997, 18 (03): : 175 - 184
  • [4] ELASTASE ACTIVITY IN BRONCHOALVEOLAR LAVAGE FLUID FROM OXYGEN-EXPOSED, PSEUDOMONAS-INFECTED BABOONS
    COLLINS, JF
    ANZUETO, AA
    PETERS, JI
    DELOSSANTOS, R
    GONZALEZ, DC
    JOHANSON, WG
    SEIDENFELD, JJ
    COALSON, JJ
    JENKINSON, SG
    [J]. LUNG, 1991, 169 (03) : 165 - 179
  • [5] CROUCH E, 1994, J BIOL CHEM, V269, P17311
  • [6] Surfactant proteins A and D and pulmonary host defense
    Crouch, E
    Wright, JR
    [J]. ANNUAL REVIEW OF PHYSIOLOGY, 2001, 63 : 521 - 554
  • [7] Degradation of surfactant protein D by alveolar macrophages
    Dong, Q
    Wright, JR
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 1998, 274 (01) : L97 - L105
  • [8] PROTEASES OF PSEUDOMONAS-AERUGINOSA IN PATIENTS WITH CYSTIC-FIBROSIS
    DORING, G
    OBERNESSER, HJ
    BOTZENHART, K
    FLEHMIG, B
    HOIBY, N
    HOFMANN, A
    [J]. JOURNAL OF INFECTIOUS DISEASES, 1983, 147 (04) : 744 - 750
  • [9] The bronchoalveolar lavage fluid of cystic fibrosis lung transplant recipients demonstrates increased interleukin-8 and elastase and decreased IL-10
    Dosanjh, AK
    Elashoff, D
    Robbins, RC
    [J]. JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 1998, 18 (10) : 851 - 854
  • [10] Protease IV, a unique extracellular protease and virulence factor from Pseudomonas aeruginosa
    Engel, LS
    Hill, JM
    Caballero, AR
    Green, LC
    O'Callaghan, RJ
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (27) : 16792 - 16797