Accession Number:

ADA224188

Title:

Activated Macrophages Destroy Intracellular Leishmania Major Amastigotes by an l-Arginine-Dependent Killing Mechanism

Descriptive Note:

Corporate Author:

WALTER REED ARMY INST OF RESEARCH WASHINGTON DC

Report Date:

1990-01-01

Pagination or Media Count:

7.0

Abstract:

Macrophages infected with amastigotes of Leishmania major and treated with IFNg in vitro develop potent antimicrobial activities that eliminate the intracellular parasite. This antileishmanial activity was suppressed in a dose dependent fashion by NG-monomethyl-L-arginine NGMMLA, a competitive inhibitor of nitrite, nitric oxide and L-citrulline synthesis from L-arginine. Excess L- arginine added to infected macrophage cultures reversed the inhibitory effects of NGMMLA. Addition of arginase to culture media inhibited intracellular killing by IFNg-treated cells. Similar effects were seen with macrophages obtained from BCG-infected C3HHeN mice. Increased levels of nitrite, an oxidative product of the L-arginine dependent effector mechanism, was measured in cultures of infected IFNg-treated macrophages as well as infected BCG-activated macrophages. Nitrite production correlated with development of antileishmanial activity. Nitrite production and microbicidal activity both decreased when in vivo or in vitro-activated macrophages were cultured in the presence of either arginase or NGMMLA. Nitric oxide synthesized from a terminal guanidino nitrogen atom of L- arginine and a precursor of the nitrite measured, may disrupt Fe-dependent enzymatic pathways vital to the survival of amastigotes within macrophages. Reprints.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE