HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 103/4/1386    most recent 00312.2007v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gonzalez, N. C. Articles by Wood, J. G. Search for Related Content PubMed PubMed Citation Articles by Gonzalez, N. C. Articles by Wood, J. G.

Alveolar macrophages are necessary for the systemic inflammation of acute alveolar hypoxia

¹Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas; and ²Department of Molecular Cell Biology, Vrije Universiteit, Faculty of Medicine, Amsterdam, The Netherlands

Submitted 19 March 2007 ; accepted in final form 16 July 2007

Alveolar hypoxia (FI_O2 0.10) rapidly produces inflammation in the microcirculation of skeletal muscle, brain, and mesentery of rats. Dissociation between tissue PO₂ values and inflammation, plus the observation that plasma from hypoxic rats activates mast cells and elicits inflammation in normoxic tissues, suggest that the response to hypoxia is initiated when mast cells are activated by an agent released from a distant site and carried by the circulation. These experiments tested the hypothesis that this agent originates in alveolar macrophages (AM). Male rats were depleted of AM by tracheal instillation of clodronate-containing liposomes. Four days after treatment, AM recovered by bronchoalveolar lavage were <10% of control. Control rats received buffer-containing liposomes. As expected, alveolar hypoxia (FI_O2 0.10) in control rats increased leukocyte-endothelial adherence, produced degranulation of perivascular mast cells, and increased fluorescent albumin extravasation in the cremaster microcirculation. None of these effects was seen when AM-depleted rats were exposed to hypoxia. Plasma obtained from control rats after 5 min of breathing 10% O₂ elicited inflammation when applied to normoxic cremasters. In contrast, normoxic cremasters did not develop inflammation after application of plasma from hypoxic AM-depleted rats. Supernatant from AM cultured in 10% O₂ produced increased leukocyte-endothelial adherence, vasoconstriction, and albumin extravasation when applied to normoxic cremasters. Normoxic AM supernatant did not produce any of these responses. The effects of hypoxic supernatant were attenuated by pretreatment of the cremaster with the mast cell stabilizer cromolyn. These data support the hypothesis that AM are the source of the agent that initiates hypoxia-induced systemic inflammation by activating mast cells.

microcirculation; leukocyte-endothelial interactions; reduced inspired oxygen

This article has been cited by other articles:

				J. Chao, J. G. Wood, V. G. Blanco, and N. C. Gonzalez The Systemic Inflammation of Alveolar Hypoxia Is Initiated by Alveolar Macrophage-Borne Mediator(s) Am. J. Respir. Cell Mol. Biol., November 1, 2009; 41(5): 573 - 582. [Abstract] [Full Text] [PDF]