Figure 1

Schematic representation of the systemic inflammation of hypoxia. Reduced alveolar PO₂ activates alveolar macrophages (AMØ) but not peripheral tissue resident macrophages (Tissue MØ) or mast cells. Activated AMØ release H₂O₂ which is the product of dismutation of O₂ ^- generated during the respiratory burst. AMØ stimulation leads to release of monocyte chemoattranctant protein-1 (MCP-1), a chemokine with mast cell secretagogue properties. Hypoxia-induced release of additional mediators by AMØ can not be ruled out. The mediator is trasported by circulation and activates mast cells. Activation of mast cells is evidenced by degranulation and by generation of reactive O₂ species (ROS) and reduction of NO levels. Mast cell activation leads to microvascular inflammation charcterized by increased leukocyte-endothelial adhesive interactions, leukocyte emigration and increased vascular permeability. The renin-angiotensin system (RAS) is activated by mast cell degranulation and participates in the production of the inflammation, although participation of other mast cell-borne mediators (histamine) can not be ruled out. ROS generation is detected in the endothelial layer of post-capillary venules as well in the sites of adhesion of leukocytes.