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Infection and Immunity, October 2000, p. 5991-5997, Vol. 68, No. 10
Department of Host Defense, Osaka City
University Graduate School of Medicine, 1-4-3 Asahi-machi,
Abeno-ku, Osaka 545-8585,1 and
Department of Pathology, Showa University College of
Medical Sciences, 1865 Tokaichiba-machi, Midori-ku, Yokohama
226-8555,2 Japan
Received 10 April 2000/Returned for modification 5 May
2000/Accepted 12 July 2000
Neovascularization or angiogenesis is required for the progression
of chronic inflammation. The mechanism of inflammatory neovascularization in tuberculosis remains unknown. Trehalose 6,6'-dimycolate (TDM) purified from Mycobacterium
tuberculosis was injected into rat corneas. TDM challenge
provoked a local granulomatous response in association with
neovascularization. Neovascularization was seen within a few days after
the challenge, with the extent of neovascularization being dose
dependent, although granulomatous lesions developed 14 days after the
challenge. Cytokines, including tumor necrosis factor alpha (TNF-
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Trehalose 6,6'-Dimycolate (Cord Factor) of Mycobacterium
tuberculosis Induces Corneal Angiogenesis in Rats
),
interleukin-8 (IL-8), IL-1
, and vascular endothelial growth factor
(VEGF), were found in lesions at the early stage (within a few days
after the challenge) and were detectable until day 21. Neovascularization was inhibited substantially by neutralizing
antibodies to VEGF and IL-8 but not IL-1
. Treatment with
anti-TNF-
antibodies resulted in partial inhibition. TDM possesses
pleiotropic activities, and the cytokine network plays an important
role in the process of neovascularization.
*
Corresponding author. Mailing address: Department
of Host Defense, Osaka City University Graduate School of
Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. Phone:
81-6-6645-3746. Fax: 81-6-6645-3747. E-mail:
nsaita{at}msic.med.osaka-cu.ac.jp.
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