Figure 8.

Proposed model for the mechanisms of action of PAR₄-mediated oedema formation. In the blood vessel depicted schematically, we propose that PAR₄ activation could occur both on endothelial cells and neutrophils to affect vascular permeability (1). Activated neutrophils would release tissue kallikrein activity (2). Tissue kallikrein would then cleave kininogens found at the surface of neutrophils and endothelial cells to produce active kinins (3). These kinins would in turn bind to and activate endothelial B₂ receptors to increase vascular permeability, resulting in oedema and the migration of neutrophils into the tissue (4). With the breach of endothelial integrity, plasma kallikrein could then add to the response following activation of the contact system (5). TK, tissue kallikrein; PK, plasma kallikrein; BK, bradykinin.