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Mast cells mediate the microvascular inflammatory response to systemic hypoxia
Dawn R S Steiner1, Norberto C Gonzalez, John G Wood
1Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City 66160, USA.
Journal of Applied Physiology (Bethesda, Md. : 1985)
|October 23, 2002
Summary
Systemic hypoxia triggers inflammation by activating mast cells, leading to increased reactive oxygen species (ROS) and leukocyte activity. Blocking mast cell degranulation reduces these inflammatory responses, highlighting their crucial role.
Area of Science:
- Physiology
- Immunology
- Microcirculation
Background:
- Systemic hypoxia induces inflammation, characterized by reactive oxygen species (ROS), leukocyte adhesion, and increased vascular permeability.
- Inflammation is often initiated by mediators from activated perivascular cells, driving leukocyte accumulation.
- The role of mast cells in hypoxia-induced microvascular inflammation requires further investigation.
Purpose of the Study:
- To investigate the potential involvement of mast cells in the microvascular inflammatory response to systemic hypoxia.
- To examine the effects of hypoxia on mast cell degranulation, ROS production, leukocyte-endothelial interactions, and vascular permeability.
Main Methods:
- Intravital microscopy was employed in anesthetized rats to study the mesenteric microcirculation.
- Mast cell degranulation was induced using compound 48/80 and studied under normoxic and hypoxic conditions.
- Measurements included reactive oxygen species (ROS) levels, leukocyte adherence and emigration, and vascular permeability.
- Pharmacological interventions, including cromolyn (mast cell stabilizer), lipoic acid (antioxidant), and nitric oxide, were used to block mast cell degranulation.
Main Results:
- Hypoxia induced rapid mast cell degranulation in the mesenteric microcirculation.
- Blocking mast cell degranulation with cromolyn attenuated hypoxia-induced increases in ROS, leukocyte adherence/emigration, and vascular permeability.
- Mast cell degranulation during hypoxia was inhibited by the antioxidant lipoic acid and nitric oxide administration.
- Mast cell activation with compound 48/80 mimicked some, but not all, effects of hypoxia.
Conclusions:
- Mast cells play a pivotal role in mediating microvascular inflammation induced by systemic hypoxia.
- The balance between reactive oxygen species (ROS) and nitric oxide may be critical for mast cell activation during hypoxic conditions.
- Targeting mast cell activation presents a potential therapeutic strategy for managing hypoxia-induced inflammation.