Hypoxemia in the absence of blood loss upregulates iNOS expression and activity in macrophages

Martin K. Angele, Martin G Schwacha, Nadia Smail, Robert A. Catania, Alfred Ayala, William G. Cioffi, Irshad H. Chaudry

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Regional hypoxia, associated with hemorrhage, is thought to induce a variety of alterations in immune cell function, including upregulation of macrophage-inducible nitric oxide synthase (iNOS) expression and activity (NO production). Furthermore, NO may cause immune cell dysfunction similar to that associated with hemorrhagic shock. However, it remains unknown whether hypoxia per se in the absence of any blood loss is a sufficient stimulus to cause iNOS expression and NO production by macrophages. To study this, male Sprague-Dawley rats (275-325 g) were placed in a plastic box flushed with a gas mixture containing 5% O2-95% N2 for 60 min. Peritoneal and splenic macrophages were isolated 0-5.5 h thereafter, and blood samples were obtained. Nitrite and nitrate (stable degradation products of NO) production by splenic and peritoneal macrophages cultured for 48 h was significantly increased 3 and 5.5 h after hypoxemia. The increase in NO production by macrophages was preceded by elevated expression of iNOS mRNA at 1.5 h after hypoxia. Additionally, interferon-γ (IFN-γ) levels in plasma from rats subjected to hypoxemia were significantly elevated soon after the insult (0- 1.5 h posthypoxemia), suggesting a causal relationship between IFN-γ production and upregulation of iNOS activity. We propose that a hypoxemia- induced increase in macrophage iNOS activity following hemorrhage may in part be responsible for the observed immune dysfunction. Thus attempts to suppress macrophage iNOS activity after this form of trauma may be helpful in improving immune function under those conditions.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume276
Issue number2 45-2
StatePublished - 1999
Externally publishedYes

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Macrophages
Nitric Oxide Synthase Type II
Blood
Up-Regulation
Peritoneal Macrophages
Interferons
Rats
Hemorrhage
Hemorrhagic Shock
Nitrites
Nitrates
Plastics
Sprague Dawley Rats
Hypoxia
Gas mixtures
Gases
Messenger RNA
Plasmas
Wounds and Injuries
Degradation

Keywords

  • Hemorrhagic shock
  • Inducible nitric oxide synthase
  • Interferon
  • Nitric oxide
  • Peritoneal macrophages
  • Splenic macrophages

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Angele, M. K., Schwacha, M. G., Smail, N., Catania, R. A., Ayala, A., Cioffi, W. G., & Chaudry, I. H. (1999). Hypoxemia in the absence of blood loss upregulates iNOS expression and activity in macrophages. American Journal of Physiology - Cell Physiology, 276(2 45-2).

Hypoxemia in the absence of blood loss upregulates iNOS expression and activity in macrophages. / Angele, Martin K.; Schwacha, Martin G; Smail, Nadia; Catania, Robert A.; Ayala, Alfred; Cioffi, William G.; Chaudry, Irshad H.

In: American Journal of Physiology - Cell Physiology, Vol. 276, No. 2 45-2, 1999.

Research output: Contribution to journalArticle

Angele, Martin K. ; Schwacha, Martin G ; Smail, Nadia ; Catania, Robert A. ; Ayala, Alfred ; Cioffi, William G. ; Chaudry, Irshad H. / Hypoxemia in the absence of blood loss upregulates iNOS expression and activity in macrophages. In: American Journal of Physiology - Cell Physiology. 1999 ; Vol. 276, No. 2 45-2.
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