Elastase-producing Pseudomonas aeruginosa degrade plasma proteins and extracellular products of human skin and fibroblasts, and inhibit fibroblast growth

被引:87
作者
Schmidtchen, A
Holst, E
Tapper, H
Björck, L
机构
[1] Lund Univ, Biomed Ctr B14, Dept Med Microbiol Dermatol & Infect, Dermatol Sect, S-22184 Lund, Sweden
[2] Lund Univ, Dept Med Microbiol Dermatol & Infect, Sect Med Microbiol, S-22184 Lund, Sweden
[3] Lund Univ, Dept Cell & Mol Biol, Sect Mol Pathogenesis, Lund, Sweden
关键词
bacteria; connective tissue; proteoglycan; wound healing;
D O I
10.1016/S0882-4010(02)00197-3
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Leg ulcers of venous origin represent a disease affecting 0.1-0.2% of the population. It is known that almost all chronic ulcers are colonized by different bacteria, such as staphylococci, enterococci and Pseudomonas aeruginosa. We here report that P. aeruginosa, expressing the major metalloproteinase elastase, induces degradation of complement C3, various antiproteinases, kininogens, fibroblast proteins, and proteoglycans (PG) in vitro, thus mimicking proteolytic activity previously identified in chronic ulcer fluid in vivo. Elastase-producing P. aeruginosa isolates were shown to significantly degrade human wound fluid as well as human skin proteins ex vivo. Elastase-containing conditioned P. aeruginosa medium and purified elastase inhibited fibroblast cell growth. These effects, in conjunction with the finding that proteinase production was detected in wound fluid ex vivo, suggest that bacterial proteinases play a pathogenic role in chronic ulcers. (C) 2003 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:47 / 55
页数:9
相关论文
共 51 条
[1]  
Ågren MS, 2000, ACTA DERM-VENEREOL, P3
[2]   Virulence factors from Pseudomonas aeruginosa increase lung epithelial permeability [J].
Azghani, AO ;
Miller, EJ ;
Peterson, BT .
LUNG, 2000, 178 (05) :261-269
[3]   ETIOLOGY OF CHRONIC LEG ULCERS [J].
BAKER, SR ;
STACEY, MC ;
SINGH, G ;
HOSKIN, SE ;
THOMPSON, PJ .
EUROPEAN JOURNAL OF VASCULAR SURGERY, 1992, 6 (03) :245-251
[4]   STREPTOCOCCAL PROTEIN-G, EXPRESSED BY STREPTOCOCCI OR BY ESCHERICHIA-COLI, HAS SEPARATE BINDING-SITES FOR HUMAN-ALBUMIN AND IGG [J].
BJORCK, L ;
KASTERN, W ;
LINDAHL, G ;
WIDEBACK, K .
MOLECULAR IMMUNOLOGY, 1987, 24 (10) :1113-1122
[5]   TISSUE INHIBITOR OF METALLOPROTEINASES-1 IS DECREASES AND ACTIVATED GELATINASES ARE INCREASED IN CHRONIC WOUNDS [J].
BULLEN, EC ;
LONGAKER, MT ;
UPDIKE, DL ;
BENTON, R ;
LADIN, D ;
HOU, ZZ ;
HOWARD, EW .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1995, 104 (02) :236-240
[6]   Activation of a 66-kilodalton human endothelial cell matrix metalloprotease by Streptococcus pyogenes extracellular cysteine protease [J].
Burns, EH ;
Marciel, AM ;
Musser, JM .
INFECTION AND IMMUNITY, 1996, 64 (11) :4744-4750
[7]   INHIBITION OF PSEUDOMONAS-AERUGINOSA ELASTASE AND PSEUDOMONAS KERATITIS USING A THIOL-BASED PEPTIDE [J].
BURNS, FR ;
PATERSON, CA ;
GRAY, RD ;
WELLS, JT .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1990, 34 (11) :2065-2069
[8]   PATHOGENESIS AND THERAPY OF PSEUDOMONAS-AERUGINOSA KERATITIS [J].
DART, JKG ;
SEAL, DV .
EYE, 1988, 2 :S46-S55
[9]   Use of molecular techniques to study microbial diversity in the skin: Chronic wounds reevaluated [J].
Davies, CE ;
Wilson, MJ ;
Hill, KE ;
Stephens, P ;
Hill, CM ;
Harding, KG ;
Thomas, DW .
WOUND REPAIR AND REGENERATION, 2001, 9 (05) :332-340
[10]   Pseudomonas aeruginosa virulence factors delay airway epithelial wound repair by altering the actin cytoskeleton and inducing overactivation of epithelial matrix metalloproteinase-2 [J].
de Bentzmann, S ;
Polette, M ;
Zahm, JM ;
Hinnrasky, J ;
Kileztky, C ;
Bajolet, O ;
Klossek, JM ;
Filloux, A ;
Lazdunski, A ;
Puchelle, E .
LABORATORY INVESTIGATION, 2000, 80 (02) :209-219