title: Cross-talk between the complement and the kinin system in vascular permeability.
abstract: The endothelium is a continuous physical barrier that regulates coagulation and selective passage of soluble molecules and circulating cells through the vessel wall into the tissue. Due to its anatomic localization, the endothelium may establish contact with components of the complement, the kinin and the coagulation systems which are the main, though not exclusive, inducers of vascular leakage. Although the complement and the kinin systems may act independently, increasing evidence suggest that there is a crosstalk that involve different components of both systems. Activation is required for the function of the two systems which are involved in pathological conditions such as hereditary and acquired angioedema (AE) and vasculitidis. The aim of this review is to discuss the contribution of complement and kinin systems to vascular leakage and the cross-talk between the two systems in the development of AE. This clinical condition is characterized by episodic and recurrent local edema of subcutaneous and submucosal tissues and is due to inherited or acquired C1-INH deficiency. Although the pathogenesis of the swelling in patients with AE was originally thought to be mediated by C2, ample evidence indicate bradykinin (BK) as the most effective mediator even though the possibility that both the complement and the kinin-forming systems may contribute to the edema has not been completely excluded. BK induces endothelial leakage interacting with B2 receptors but other molecules may be involved in the onset and maintenance of AE. In this review we shall discuss the role of B1 receptors and gC1qR/p33 in addition to that of B2 receptors in the onset of AE attacks and the importance of these receptors as new possible molecular targets for therapy.
authors.affiliation: Department of Life Sciences, University of Trieste, via Valerio 28, 34127 Trieste, Italy.
authors.forename: Fleur
authors.initials: F
authors.lastname: Bossi
authors.forename: Ellinor I
authors.initials: EI
authors.lastname: Peerschke
authors.forename: Berhane
authors.initials: B
authors.lastname: Ghebrehiwet
authors.forename: Francesco
authors.initials: F
authors.lastname: Tedesco
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000276:immunology*; D002199:Capillary Permeability / Q000276:immunology; D003167:Complement Activation; D003165:Complement System Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D056829:Hereditary Angioedema Types I and II / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D058990:Molecular Targeted Therapy / Q000639:trends; D020239:Receptor Cross-Talk; D018002:Receptors, Bradykinin / Q000276:immunology / Q000378:metabolism*
chemical_list: D018002:Receptors, Bradykinin; D003165:Complement System Proteins; D001920:Bradykinin