Nitric oxide. A macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells. Academic Article uri icon

Overview

abstract

  • A metabolic pathway of activated macrophages (M phi) involving oxidation of the guanido nitrogens of L-arginine is required for inhibition of growth and respiration of some target cells. The goal of this study was to identify the M phi metabolite(s) that induce these injuries. The stable products of the L-arginine pathway, NO2- and NO3-, were incapable of causing cytostasis under coculture conditions. However, NO2- became cytostatic upon mild acidification, which favors its transformation into nitrogen oxides of greater reactivity. This suggested that NO. (and/or NO2), recently identified as an M phi metabolite of L-arginine, could be a mediator. Authentic NO. caused cytostasis and respiratory inhibition in L1210 cells in a dose-dependent manner. The mitochondrial lesions caused by NO. were confined to complex 1 and 2, a pattern of injury identical to that seen after coculture with activated M phi. Inclusion of NO. scavenger systems prevented cytostasis from developing in M phi-L1210 cocultures. Thus, M phi-generated NO. can account for L-arginine-dependent cytostasis and respiratory inhibition.

publication date

  • May 1, 1989

Research

keywords

  • Leukemia L1210
  • Macrophages
  • Nitric Oxide

Identity

PubMed Central ID

  • PMC2189318

Scopus Document Identifier

  • 0024584020

PubMed ID

  • 2497225

Additional Document Info

volume

  • 169

issue

  • 5