This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Feng, H. M. Articles by Walker, D. H. Search for Related Content PubMed PubMed Citation Articles by Feng, H. M. Articles by Walker, D. H.

American Journal of Pathology, Vol 143, 1016-1023, Copyright © 1993 by American Society for Investigative Pathology

REGULAR ARTICLES

Interferon-gamma and tumor necrosis factor-alpha exert their antirickettsial effect via induction of synthesis of nitric oxide

HM Feng and DH Walker
Department of Pathology, University of Texas Medical Branch, Galveston 77555-0609.

How the host defenses control rickettsiae in the cytosol of nonphagocytic host cells, where they are not exposed to antibodies or phagocytes, has posed a difficult question. Rickettsia conorii infection of a mouse fibroblast cell line was inhibited in a dose- dependent manner by nitrogen oxide synthesized by eukaryotic host cells stimulated by interferon-gamma or tumor necrosis factor-alpha. L- arginine was the source of the nitric oxide as demonstrated by competitive inhibition by NG-monomethyl-L-arginine. Nitric oxide synthesis required host cell protein synthesis and had an approximately 48-hour lag phase following cytokine stimulation. At low doses of interferon-gamma and tumor necrosis factor-alpha, which had no detectable response as single agents, dramatic synergistic nitric oxide synthesis and antirickettsial effects were observed.

This article has been cited by other articles:

				R. Fang, N. Ismail, L. Soong, V. L. Popov, T. Whitworth, D. H. Bouyer, and D. H. Walker Differential Interaction of Dendritic Cells with Rickettsia conorii: Impact on Host Susceptibility to Murine Spotted Fever Rickettsiosis Infect. Immun., June 1, 2007; 75(6): 3112 - 3123. [Abstract] [Full Text] [PDF]

				D. Howe, L. F. Barrows, N. M. Lindstrom, and R. A. Heinzen Nitric Oxide Inhibits Coxiella burnetii Replication and Parasitophorous Vacuole Maturation Infect. Immun., September 1, 2002; 70(9): 5140 - 5147. [Abstract] [Full Text] [PDF]

				H.-M. Feng and D. H. Walker Mechanisms of Intracellular Killing of Rickettsia conorii in Infected Human Endothelial Cells, Hepatocytes, and Macrophages Infect. Immun., December 1, 2000; 68(12): 6729 - 6736. [Abstract] [Full Text] [PDF]

				J. Turco, H. Liu, S. F. Gottlieb, and H. H. Winkler Nitric Oxide-Mediated Inhibition of the Ability of Rickettsia prowazekii To Infect Mouse Fibroblasts and Mouse Macrophagelike Cells Infect. Immun., February 1, 1998; 66(2): 558 - 566. [Abstract] [Full Text] [PDF]