Abstract
Lipoteichoic acid (LTA), the cell wall component of Gram-positive bacteria, has been shown to cause inflammatory responses comparable to lipopolysaccharide (LPS) of Gram-negative bacteria. This study examined the activity of LTA to induce dermal microvascular permeability changes in mice. Vascular permeability was assessed by extravasation of Pontamine sky blue. Subcutaneous injection of LTA (200–400 μg/site) in mice that were preinjected i.v. with the dye increased local dye leakage in the skin at 1 to 3 h. The LTA-induced dye leakage was inhibited by indomethacin, valeryl salicylate, diphenhydramine, and a platelet-activating factor antagonist but not by inhibitors of nitric-oxide synthase, cyclooxygenase-2, or guanylate cyclase or by antibodies against tumor necrosis factor-α or interleukin-1α. LTA induced comparable increases in dye leakage in inducible nitric-oxide synthase-deficient mice and wild-type controls. Pretreatment of normal mice with i.v. LTA did not confer tolerance to LTA- or LPS-induced dye leakage. In contrast, systemic LPS administration induced tolerance against subsequent challenge with LPS but not LTA. Serum corticosterone levels, which were suggested to induce tolerance, were not increased by LTA pretreatment but were increased by LPS. Thus, LTA increases dermal microvascular permeability in mice. Among the inflammatory mediators, eicosanoids, platelet-activating factor, and histamine mediate the effect of both LTA and LPS, whereas nitric oxide, tumor necrosis factor-α, and interleukin-1α may not play a major role in LTA-induced dye leakage. The difference between LTA and LPS to stimulate corticosterone may partially explain the failure of LTA to induce tolerance against vascular dye leakage.
Footnotes
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Send reprint requests to: Dr. Keiji Wada, Department of Pharmacology, Tokyo Women's Medical University, School of Medicine, 8-1, Kawada-cho Shinjuku-ku, Tokyo 162-8666 Japan. E-mail:wada-kj{at}pop12.odn.ne.jp
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↵1 This study was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture, Japan (10672158, 09672336).
- Abbreviations:
- LPS
- lipopolysaccharide
- LTA
- lipoteichoic acid
- NO
- nitric oxide
- iNOS
- inducible NO synthase
- PAF
- platelet-activating factor
- COX
- cyclooxygenase
- l-NAME
- NG-nitro-l-arginine methyl ester
- PG
- prostaglandin
- LY83583
- 6-amino-5,8-quinolinedione
- TCV309
- 3-bromo-5-[N-phenyl-N-[2-[[2-(1,2,3,4-tetrahydro-2-isoquinolyl-cabonyloxy)-ethyl]carbamoyl]ethyl]carbamoyl]-1-propylpyridinium nitrate
- NS-398
- N-(2-cyclohexyloxy-4-nitrophenyl)- methanesulphonamide
- WEB2086
- 3-[4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f]-[1,2,4]triazolo-[4,3-a][1,4]-diazepine-2-yl]-1-(4-morphonilyl)-1-propanone
- WEB2170
- 6-(2-chlorophenyl)-8,9-dihydro-1-methyl-8-(4-morphonilyl)carbonyl-4H,7H-cyclopenta[4,5]thieno[3,5-f][1,2,4]triazolo[4,3-a][1,4]diazepine
- TLR
- Toll-like receptor
- TNF
- tumor necrosis factor
- IL
- interleukin
- PSB
- Pontamine sky blue
- Received December 8, 1999.
- Accepted March 27, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
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