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Infection and Immunity, November 1998, p. 5520-5526, Vol. 66, No. 11
Graduate Institute of Immunology, College of
Medicine, National Taiwan University, Taipei, Taiwan, Republic of
China
Received 23 February 1998/Returned for modification 9 April
1998/Accepted 11 August 1998
Splenic macrophages from Histoplasma
capsulatum-infected mice express inducible nitric oxide synthase
(iNOS), and the iNOS expression correlates with severity of the
infection. We examined whether production of NO is responsible for
apoptosis and the anti-lymphoproliferative response of splenocytes from
mice infected with H. capsulatum. In situ terminal
deoxynucleotidyl transferase nick end labeling revealed apoptotic
nuclei in cryosections of spleen from infected but not normal mice.
Splenocytes of infected mice were unresponsive to stimulation by either
concanavalin A or heat-killed H. capsulatum yeast
cells. Splenocyte responsiveness was restored by addition to the medium
of NG-monomethyl-L-arginine, a
known inhibitor of NO production. The proliferative response of
splenocytes from infected mice was also restored by depletion of
macrophages or by replacement with macrophages from normal mice. In
addition, expression of iNOS returned to its basal level when the
animals had recovered from infection. These results suggest that
suppressor cell activity of macrophages is associated with production
of NO, which also appears to be an effector molecule for apoptosis of
cultured splenocytes from infected mice.
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Nitric Oxide Synthase Expression in Macrophages of
Histoplasma capsulatum-Infected Mice Is Associated with
Splenocyte Apoptosis and Unresponsiveness
*
Corresponding author. Mailing address: Graduate
Institute of Immunology, College of Medicine, National Taiwan
University, No. 1 Jen-Ai Rd., Section 1, Taipei 100, Taiwan, Republic
of China. Phone: 886-2-321-7510. Fax: 886-2-2321-7921. E-mail:
wuhsiehb{at}ha.mc.ntu.edu.tw.
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