title: Activation of mast cells by systemic hypoxia, but not by local hypoxia, mediates increased leukocyte-endothelial adherence in cremaster venules.
abstract: Systemic hypoxia, produced by lowering inspired Po2, induces a rapid inflammation in several microcirculations, including cremaster muscle. Mast cell activation is a necessary element of this response. Selective reduction of cremaster microvascular Po2 (PmO2) with normal systemic arterial Po2 (PaO2; cremaster hypoxia/systemic normoxia), however, does not elicit increased leukocyte-endothelial adherence (LEA) in cremaster venules. This could be due to a short time of leukocyte exposure to the hypoxic cremaster environment. Conversely, LEA increases when PaO2 is lowered, while cremaster PmO2 remains high (cremaster normoxia/systemic hypoxia). An alternative explanation of these results is that a mediator released from a central site during systemic hypoxia initiates the inflammatory cascade. We hypothesized that if this is the case, cremaster mast cells would be activated during cremaster normoxia/systemic hypoxia, but not during cremaster hypoxia/systemic normoxia. The microcirculation of rat cremaster muscles was visualized by using intravital microscopy. Cremaster PmO2 was measured with a phosphorescence quenching method. Cremaster hypoxia/systemic normoxia (PmO2 7 +/- 1 Torr, PaO2 87 +/- 2 Torr) did not increase LEA; however, topical application of the mast cell activator compound 48/80 under these conditions did increase LEA. The effect of compound 48/80 on LEA was blocked by topical cromolyn, a mast cell stabilizer. LEA increased during cremaster normoxia/systemic hypoxia, (PmO2 64 +/- 5 Torr, PaO2 33 +/- 2 Torr); this increase was blocked by topical cromolyn. The results suggest that mast cell stimulation occurs only when PaO2 is reduced, independent of cremaster PmO2, and support the idea of a mediator that is released during systemic hypoxia and initiates the inflammatory cascade.
authors.affiliation: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Randy
authors.initials: R
authors.lastname: Dix
authors.forename: Teresa
authors.initials: T
authors.lastname: Orth
authors.forename: Julie
authors.initials: J
authors.lastname: Allen
authors.forename: John G
authors.initials: JG
authors.lastname: Wood
authors.forename: Norberto C
authors.initials: NC
authors.lastname: Gonzalez
mesh_terms: D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology; D002448:Cell Adhesion / Q000502:physiology; D015550:Cell Degranulation / Q000187:drug effects; D004205:Cromolyn Sodium / Q000494:pharmacology; D042783:Endothelial Cells / Q000502:physiology*; D000860:Hypoxia / Q000503:physiopathology*; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D018482:Muscle, Skeletal / Q000098:blood supply*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014699:Venules / Q000166:cytology
chemical_list: D018927:Anti-Asthmatic Agents; D004205:Cromolyn Sodium