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Infection and Immunity, November 1998, p. 5520-5526, Vol. 66, No. 11
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

Betty A. Wu-Hsieh,* Wen Chen, and Hsin-Ju Lee

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.


* 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.


Infection and Immunity, November 1998, p. 5520-5526, Vol. 66, No. 11
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.



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