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Alveolar Hypoxia-Induced Systemic Inflammation: What Low PO2 Does and Does Not Do

  • Norberto C. Gonzalez
  • John G. Wood
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 662)

Abstract

Reduction of alveolar PO2 (alveolar hypoxia, AH) may occur in pulmonary diseases such as chronic obstructive pulmonary disease (COPD), or in healthy individuals ascending to altitude. Altitude illnesses may develop in non-acclimatized persons who ascend rapidly. The mechanisms underlying these illnesses are not well understood, and systemic inflammation has been suggested as a possible contributor. Similarly, there is evidence of systemic inflammation in the systemic alterations present in COPD patients, although its role as a causative factor is not clear.

We have observed that AH, induced by breathing 10% O2 produces a rapid (minutes) and widespread micro vascular inflammation in rats and mice. This inflammation has been observed directly in the mesenteric, skeletal muscle, and pial microcirculations. The inflammation is characterized by mast cell degranulation, generation of reactive O2 species, reduced nitric oxide levels, increased leukocyte-endothelial adherence in post-capillary venules, and extravasation of albumin. Activated mast cells stimulate the renin-angiotensin system (RAS) which leads to the inflammatory response via activation of NADPH oxidase. If the animals remain in hypoxia for several days, the inflammation resolves and exposure to lower PO2 does not elicit further inflammation, suggesting that the vascular endothelium has “acclimatized” to hypoxia.

Recent experiments in cremaster microcirculation suggest that the initial trigger of the inflammation is not the reduced tissue PO2, but rather an intermediary re-leased by alveolar macrophages into the circulation. The putative intermediary ac-tivates mast cells, which, in turn, stimulate the local renin-angiotensin system and induce inflammation.

Keywords

Chronic Obstructive Pulmonary Disease Mast Cell Chronic Obstructive Pulmonary Disease Patient Mast Cell Degranulation Acute Mountain Sickness 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

Supported by National Institutes of Health, USA, grant HL39443

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Molecular and Integrative PhysiologyUniversity of Kansas Medical CenterKansas CityUSA

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