Osteopontin promotes host defense during Klebsiella pneumoniae-induced pneumonia

被引:26
作者
van der Windt, G. J. W. [2 ,3 ]
Hoogerwerf, J. J. [2 ,3 ]
de Vos, A. F. [2 ,3 ]
Florquin, S. [1 ]
van der Poll, T. [1 ,3 ]
机构
[1] Univ Amsterdam, Acad Med Ctr, Dept Pathol, NL-1105 AZ Amsterdam, Netherlands
[2] Univ Amsterdam, Ctr Infect & Immun Amsterdam CINIMA, NL-1105 AZ Amsterdam, Netherlands
[3] Univ Amsterdam, Ctr Expt & Mol Med, NL-1105 AZ Amsterdam, Netherlands
关键词
Infection; Klebsiella pneumoniae; lung; mice; osteopontin; TOLL-LIKE RECEPTOR-4; NEUTROPHIL RECRUITMENT; CXC CHEMOKINE; CD44; EXPRESSION; MACROPHAGES; DISEASE; LUNGS; MODEL;
D O I
10.1183/09031936.00002710
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
Klebsiella pneumoniae is a common cause of nosocomial pneumonia. Osteopontin (OPN) is a phosphorylated glycoprotein involved in inflammatory processes, some of which is mediated by CD44. The aim of this study was to determine the role of OPN during K. pneumoniae-induced pneumonia. Wild-type (WT) and OPN knockout (KO) mice were intranasally infected with 10(4) colony forming units of K. pneumoniae, or administered Klebsiella lipopolysaccharides (LPS). In addition, recombinant OPN (rOPN) was intranasally administered to WT and CD44 KO mice. During Klebsiella pneumonia, WT mice displayed elevated pulmonary and plasma OPN levels. OPN KO and WT mice showed similar pulmonary bacterial loads 6 h after infection; thereafter, Klebsiella loads were higher in lungs of OPN KO mice and the mortality rate in this group was higher than in WT mice. Early neutrophil recruitment into the bronchoalveolar space was impaired in the absence of OPN after intrapulmonary delivery of either Klebsiella bacteria or Klebsiella LPS. Moreover, rOPN induced neutrophil migration into the bronchoalveolar space, independent from CD44. In vitro, OPN did not affect K. pneumoniae growth or neutrophil function. In conclusion, OPN levels were rapidly increased in the bronchoalveolar space during K. pneumoniae pneumonia, where OPN serves a chemotactic function towards neutrophils, thereby facilitating an effective innate immune response.
引用
收藏
页码:1337 / 1345
页数:9
相关论文
共 39 条
[1]   Polarization and directed migration of murine neutrophils is dependent on cell surface expression of CD44 [J].
Alstergren, P ;
Zhu, BQ ;
Glougauer, M ;
Mak, TW ;
Ellen, RP ;
Sodek, J .
CELLULAR IMMUNOLOGY, 2004, 231 (1-2) :146-157
[2]  
Bainbridge Brian W, 2002, Ann Periodontol, V7, P29, DOI 10.1902/annals.2002.7.1.29
[3]   Interaction of osteopontin with neutrophil α4β1 and α9β1 integrins in a rodent model of alcoholic liver disease [J].
Baneijee, Atrayee ;
Lee, Jin-Hyung ;
Ramaiah, Shashi K. .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 2008, 233 (02) :238-246
[4]   Higher neutrophil infiltration mediated by osteopontin is a likely contributing factor to the increased susceptibility of females to alcoholic liver disease [J].
Banerjee, A ;
Apte, UM ;
Smith, R ;
Ramaiah, SK .
JOURNAL OF PATHOLOGY, 2006, 208 (04) :473-485
[5]   Altered bleomycin-induced lung fibrosis in osteopontin-deficient mice [J].
Berman, JS ;
Serlin, D ;
Li, XF ;
Whitley, G ;
Hayes, J ;
Rishikof, DC ;
Ricupero, DA ;
Liaw, L ;
Goetschkes, M ;
O'Regan, AW .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2004, 286 (06) :L1311-L1318
[6]   TLR9 is required for protective innate immunity in gram-negative bacterial pneumonia: Role of dendritic cells [J].
Bhan, Urvashi ;
Lukacs, Nicholas W. ;
Osterholzer, John J. ;
Newstead, Michael W. ;
Zeng, Xianying ;
Moore, Thomas A. ;
McMillan, Tracy R. ;
Krieg, Arthur M. ;
Akira, Shizuo ;
Standiford, Theodore J. .
JOURNAL OF IMMUNOLOGY, 2007, 179 (06) :3937-3946
[7]   Role of toll-like receptor 4 in gram-positive and gram-negative pneumonia in mice [J].
Branger, J ;
Knapp, S ;
Weijer, S ;
Leemans, JC ;
Pater, JM ;
Speelman, P ;
Florquin, SR ;
van der Poll, T .
INFECTION AND IMMUNITY, 2004, 72 (02) :788-794
[8]   CEFTAZIDIME RESISTANCE AMONG SELECTED NOSOCOMIAL GRAM-NEGATIVE BACILLI IN THE UNITED-STATES [J].
BURWEN, DR ;
BANERJEE, SN ;
GAYNES, RP .
JOURNAL OF INFECTIOUS DISEASES, 1994, 170 (06) :1622-1625
[9]   Both TRIF- and MyD88-Dependent Signaling Contribute to Host Defense against Pulmonary Klebsiella Infection [J].
Cai, Shanshan ;
Batra, Sanjay ;
Shen, Li ;
Wakamatsu, Nobuko ;
Jeyaseelan, Samithamby .
JOURNAL OF IMMUNOLOGY, 2009, 183 (10) :6629-6638
[10]   Persistent Elevation of Plasma Osteopontin Levels in HIV Patients Despite Highly Active Antiretroviral Therapy [J].
Chagan-Yasutan, Haorile ;
Saitoh, Hiroki ;
Ashino, Yugo ;
Arikawa, Tomohiro ;
Hirashima, Mitsuomi ;
Li, Shenwei ;
Usuzawa, Motoki ;
Oguma, Shigeru ;
Telan, Elizabeth Freda O. ;
Obi, Chikwelu Larry ;
Hattori, Toshio .
TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE, 2009, 218 (04) :285-292