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Infection and Immunity, May 1999, p. 2421-2427, Vol. 67, No. 5
Departments of Obstetrics & Gynecology,1 Microbiology & Immunology,2 and Anatomy & Neurosciences,3 The University of Texas
Medical Branch at Galveston, Galveston, Texas
Received 24 June 1998/Returned for modification 8 December
1998/Accepted 11 February 1999
The contribution of nitric oxide to host resistance to experimental
pyelonephritis is not well understood. We examined whether the
inhibition of nitric oxide synthesis alters the sensitivity of
lipopolysaccharide (LPS) responder (C3H/HeN) and nonresponder (C3H/HeJ)
mice to experimental Escherichia coli pyelonephritis. C3H/HeJ and C3H/HeN mice were implanted subcutaneously with minipumps containing an inhibitor of nitric oxide,
NG-nitro-L-arginine methyl ester
(L-NAME), or a corresponding vehicle. Ascending urinary
tract infection by bladder catheterization with two strains of E. coli, an O75 strain bearing Dr fimbriae and an O75 strain bearing
P fimbriae, was developed in tested animals. Twenty-four hours
following bladder infection, the kidneys of C3H/HeN and C3H/HeJ mice
were colonized at a similar rate. However, 5 weeks postinoculation,
C3H/HeN mice cleared infection while C3H/HeJ mice showed persistent
colonization. Twenty-four hours following infection, C3H/HeN mice
treated with L-NAME showed no significant increase of renal
tissue infection compared to the saline-treated control group. However,
L-NAME-treated C3H/HeJ mice showed an approximately
100-fold increase in E. coli infection rate compared to the
saline-treated controls in the Dr+ group but showed no
change compared to those in the P+ group. Dissemination of
Dr+ E. coli but not P+ E. coli to the liver and uterus was significantly enhanced with L-NAME treatment in C3H/HeJ mice only. Nitric oxide had no
direct killing effect on E. coli in vitro. Nitrite
production by various organs was found to be significantly lower in
C3H/HeJ mice than in C3H/HeN mice. Alteration of nitric oxide and LPS
responsiveness was significantly associated with the increased
sensitivity of C3H/HeJ mice to experimental Dr+ but not to
P+ E. coli pyelonephritis. These findings are
consistent with the hypothesis that nitric oxide synthase activity in
concert with LPS responsiveness may participate in the antibacterial
defense mechanisms of the C3H mouse urinary tract. This phenomenon is strain dependent and possibly related to the invasive properties of
E. coli.
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Inverse Relationship between Severity of
Experimental Pyelonephritis and Nitric Oxide Production in
C3H/HeJ Mice
*
Corresponding author. Dept. of Obstetrics & Gynecology,
The University of Texas Medical Branch at Galveston, 301 University Blvd., Galveston, TX 77555-1062. Phone: (409) 772-7599. Fax: (409) 747-0475. E-mail: bnowicki{at}marlin.utmb.edu.
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