title: Mast cells mediate the microvascular inflammatory response to systemic hypoxia.
abstract: Systemic hypoxia produces an inflammatory response characterized by increases in reactive O(2) species (ROS), venular leukocyte-endothelial adherence and emigration, and vascular permeability. Inflammation is typically initiated by mediators released from activated perivascular cells that generate the chemotactic gradient responsible for extravascular leukocyte accumulation. These experiments were directed to study the possible participation of mast cells in hypoxia-induced microvascular inflammation. Mast cell degranulation, ROS levels, leukocyte adherence and emigration, and vascular permeability were studied in the mesenteric microcirculation by using intravital microscopy of anesthetized rats. The main findings were 1) activation of mast cells with compound 48/80 in normoxia produced microvascular effects similar, but not identical, to those of hypoxia; 2) systemic hypoxia resulted in rapid mast cell degranulation; 3) blockade of mast cell degranulation with cromolyn prevented or attenuated the hypoxia-induced increases in ROS, leukocyte adherence/emigration, and vascular permeability; and 4) mast cell degranulation during hypoxia was prevented by administration of the antioxidant lipoic acid and of nitric oxide. These results show that mast cells play a key role in hypoxia-induced inflammation and suggest that alterations in the ROS-nitric oxide balance may be involved in mast cell activation during hypoxia.
authors.affiliation: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City 66160, USA.
authors.forename: Dawn R S
authors.initials: DR
authors.lastname: Steiner
authors.forename: Norberto C
authors.initials: NC
authors.lastname: Gonzalez
authors.forename: John G
authors.initials: JG
authors.lastname: Wood
mesh_terms: D000818:Animals; D002199:Capillary Permeability; D002448:Cell Adhesion; D015550:Cell Degranulation / Q000187:drug effects; D002465:Cell Movement; D004205:Cromolyn Sodium / Q000494:pharmacology; D000860:Hypoxia / Q000150:complications* / Q000503:physiopathology*; D007962:Leukocytes / Q000502:physiology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D008833:Microcirculation; D009569:Nitric Oxide / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000097:blood; D013152:Splanchnic Circulation; D014657:Vasculitis / Q000209:etiology*; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
chemical_list: D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D003189:p-Methoxy-N-methylphenethylamine; D004205:Cromolyn Sodium