Induction of indoleamine 2,3-dioxygenase in mouse lung during virus infection.

Abstract

Indoleamine 2,3-dioxygenase [indoleamine: oxygen 2,3-oxidoreductase (decyclizing)] activity in the supernatant fraction (30,000 X g, 30 min) of mouse lung homogenate increased approximately 120-fold after infection with PR8 influenza virus. Both specific and total enzyme activities started to increase linearly from the 5th day after infection, reached the highest level around the 11th day, and then gradually decreased to normal values in about 3 weeks. Other enzymes in the lung, such as certain lysosomal enzymes and monoamine oxidase, did not change significantly throughout the experiments. The time course of the increase in the enzyme activity was quite different from that of virus replication in the lung (a peak by the 3rd day and persistence until the 9th day) or that of serum antibody content (started to rise on the 9th day). Rather, it appeared to be closely related to the infiltrations of mononuclear and lymphocytic cells. When mice were exposed to a higher dose of virus and did not recuperate, the time course of the increase of the enzyme activity was essentially identical to that seen with a low concentration of virus. A maximum stimulation of the enzyme activity in the lung occurred on the 9th day after infection; the increase was approximately 100-fold. However, serum antibody content was slight and virus titer in the lung remained high. Indoleamine 2,3-dioxygenase [IDO; indoleamine:oxygen 2,3-oxidoreductase (decyclizing)] is a heme-containing enzyme (1) that catalyzes the incorporation of the superoxide anion as well as molecular oxygen (2, 3) into the pyrrole moiety of various indoleamine derivatives, such as tryptophan and serotonin (4,5). In contrast to tryptophan 2,3-dioxygenase, which catalyzes a similar reaction but is present exclusively in the liver (6), IDO is ubiquitously distributed in various organs of mammals, including brain, lung, spleen, alimentary canal, and epididymis (7), but its biological significance is not yet clearly understood. Recent studies from our laboratory demonstrated that the enzyme is dramatically induced in the mouse lung after a single intraperitoneal injection of bacterial endotoxin (8). Endotoxin, the lipopolysaccharide fraction (LPS) obtained from the cell wall of Gram-negative bacteria, is an inflammatory agent and induces nonspecific immune responses (9). The effect appeared to be specific for the pulmonary IDO activity because in all other tissues tested no significant increase in the enzyme activity was observed. In order to determine whether or not the pulmonary IDO activity is altered by specific infection of the lung, mice were exposed to PR8 influenza virus. In this paper, we report that the pulmonary IDO activity was increased more than 100-fold around the 11th day after virus infection. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact.

Indoleamine 2,3-Dioxygenase Is Regulated by IFN-γ in the Mouse Placenta DuringListeria monocytogenesInfection

“…IDO induction in macrophages has been demonstrated during viral (39) and bacterial infection (40). High activity of IDO could aid the inhibition of bacterial growth since tryptophan is often an essential amino acid for bacteria.…”

The indoleamine 2,3‐dioxygenase (IDO) pathway controls allergy

“…The invasion of bacteria, parasites, or viruses induces a strong interferon-c (IFN-c)-dependent inflammatory response. Because IFN-c is a strong IDO inducer and intracellular pathogens require trp, it was demonstrated that a depletion of free trp by IDO controls intracellular pathogens (12). A decade ago, Munn and Mellor provided evidence for a much broader immunoregulatory significance of trp degradation.…”

Impairment of Lipid Metabolism Due to Deficiency of Pyridoxal-5-phosphate and/or Activated Immune system: its Interpretation

“…IllNo. 4 induced by viruses, bacterial exotoxins and interferona (24,54). It is mentioned, that IDO takes part in the elevated kynurenine formation in pathological as well as in host defence mechanisms (54).…”