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The systemic inflammation of alveolar hypoxia is initiated by a circulating mediator(s) released from alveolar macrophages
Author(s) -
Chao Jie,
Wood John G,
Blanco V. Gustavo,
Gonzalez Norberto C.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.762.22
Subject(s) - inflammation , hypoxia (environmental) , systemic inflammation , mediator , degranulation , microcirculation , immunology , pathology , intravital microscopy , chemistry , medicine , endocrinology , receptor , oxygen , organic chemistry
Alveolar hypoxia (FIO 2 = 0.1) produces widespread systemic inflammation in rats. Recent evidence suggests that the inflammation is not triggered by the low systemic PO 2 , but by activation of mast cells (MC) by a circulating mediator released from activated alveolar macrophages (AM). If this is correct, the following should apply: 1.Neither MC nor resident tissue macrophages should be directly activated by hypoxia and 2. MC would be activated when in contact with hypoxic AM, but not with hypoxic tissue macrophages. Methods Rat mesenteric microcirculation intravital microscopy was combined with primary cultures of AM, peritoneal macrophages (PM), and peritoneal MC. Results a. Cultured peritoneal MC did not degranulate with hypoxia. b. Hypoxia induced a respiratory burst in AM, but not in PM cultures. c. Immersion of isolated MC in supernatant of hypoxic AM, but not in supernatant of hypoxic PM, induced MC degranulation d. Supernatant of hypoxic AM, but not of hypoxic PM produced MC degranulation and leukocyte‐endothelial adherence in mesentery. Conclusions A mediator(s) released from hypoxic AM activates MC and triggers the systemic inflammation. Reduced systemic tissue PO 2 and activation of systemic tissue macrophages do not play a role in this phenomenon. The inflammation may contribute to the systemic effects observed in conditions with reduced alveolar PO 2 . Supported by NIH HL39443‐18 and AHA 0815652G