The Pseudomonas aeruginosa autoinducer N-3-oxododecanoyl homoserine lactone accelerates apoptosis in macrophages and neutrophils

被引:285
作者
Tateda, K
Ishii, Y
Horikawa, M
Matsumoto, T
Miyairi, S
Pechere, JC
Standiford, TJ
Ishiguro, M
Yamaguchi, K
机构
[1] Toho Univ, Sch Med, Dept Microbiol, Tokyo 1438540, Japan
[2] Suntory Inst Bioorgan Res, Osaka 618, Japan
[3] Nihon Univ, Coll Pharm, Bioorgan Chem Lab, Chiba, Japan
[4] Univ Geneva, Dept Genet & Microbiol, Geneva, Switzerland
[5] Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA
关键词
D O I
10.1128/IAI.71.10.5785-5793.2003
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Quorum-sensing systems are critical regulators of the expression of virulence factors of various organisms, including Pseudomonas aeruginosa. Las and Rhl are two major quorum-sensing components, and they are regulated by their corresponding autoinducers, N-3-oxododecanoyl homoserine lactone (3-oxo-C-12-HSL) and N-butyryl-L-homoserine lactone (C-4-HSL). Recent progress has demonstrated the potential of quorum-sensing molecules, especially 3-oxo-C-12-HSL, for modulation of the host immune system. Here we show the specific ability of 3-oxo-C-12-HSL to induce apoptosis in certain types of cells. When bone marrow-derived macrophages were incubated with synthetic 3-oxo-C-12-HSL, but when they were incubated not C-4-HSL, significant loss of viability was observed in a concentration (12 to 50 muM)- and incubation time (1 to 24 h)-dependent manner. The cytotoxic activity of 3-oxo-C-12-HSL was also observed in neutrophils and monocytic cell lines U-937 and P388D1 but not in epithelial cell lines CCL-185 and HEp-2. Cells treated with 3-oxo-C-12-HSL revealed morphological alterations indicative of apoptosis. Acceleration of apoptosis in 3-oxo-C-12-HSL-treated cells was confirmed by multiple criteria (caspases 3 and 8, histone-associated DNA fragments, phosphatidylserine expression). Structure-activity correlation experiments demonstrated that the fine structure of 3-oxo-C-12-HSL, the HSL backbone, and side chain length are required for maximal activity. These data suggest that Pseudomonas 3-oxo-C-12-HSL specifically promotes induction of apoptosis, which may be associated with 3-oxo-C-12- HSL-induced cytotoxicity in macrophages and neutrophils. Our data suggest that the quorum-sensing molecule 3-oxo-C-12-HSL has critical roles in the pathogenesis of P. aeruginosa infection, not only in the induction of bacterial virulence factors but also in the modulation of host responses.
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页码:5785 / 5793
页数:9
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[1]   IMMUNOHISTOPATHOLOGIC LOCALIZATION OF PSEUDOMONAS-AERUGINOSA IN LUNGS FROM PATIENTS WITH CYSTIC-FIBROSIS - IMPLICATIONS FOR THE PATHOGENESIS OF PROGRESSIVE LUNG DETERIORATION [J].
BALTIMORE, RS ;
CHRISTIE, CDC ;
SMITH, GJW .
AMERICAN REVIEW OF RESPIRATORY DISEASE, 1989, 140 (06) :1650-1661
[2]   Exoenzyme S from Pseudomonas aeruginosa induces apoptosis in T lymphocytes [J].
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Buommino, E ;
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Metafora, S ;
Rossano, F ;
Perfetto, B ;
Baroni, A ;
Tufano, MA .
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de Nys, R ;
Netting, A ;
Kumar, N ;
Hentzer, M ;
Givskov, M ;
Kjelleberg, S .
ENVIRONMENTAL MICROBIOLOGY, 2000, 2 (05) :530-541
[5]   Synthetic analogues of the bacterial signal (quorum sensing) molecule N-(3-oxododecanoyl)-L-homoserine lactone as immune modulators [J].
Chhabra, SR ;
Harty, C ;
Hooi, DSW ;
Daykin, M ;
Williams, P ;
Telford, G ;
Pritchard, DI ;
Bycroft, BW .
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ZAR, HJ ;
BRYAN, R ;
PRINCE, A .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 96 (05) :2204-2210
[8]   Pseudomonas aeruginosa quorum-sensing systems may control virulence factor expression in the lungs of patients with cystic fibrosis [J].
Erickson, DL ;
Endersby, R ;
Kirkham, A ;
Stuber, K ;
Vollman, DD ;
Rabin, HR ;
Mitchell, I ;
Storey, DG .
INFECTION AND IMMUNITY, 2002, 70 (04) :1783-1790
[9]   Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-β, PGE2, and PAF [J].
Fadok, VA ;
Bratton, DL ;
Konowal, A ;
Freed, PW ;
Westcott, JY ;
Henson, PM .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (04) :890-898
[10]   Inhibition of apoptosis in Chlamydia-infected cells: Blockade of mitochondrial cytochrome c release and caspase activation [J].
Fan, T ;
Lu, H ;
Hu, H ;
Shi, LF ;
McClarty, GA ;
Nance, DM ;
Greenberg, AH ;
Zhong, GM .
JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 187 (04) :487-496