Mast cells increase vascular permeability by heparin-initiated bradykinin formation in vivo.
Immunity
; 34(2): 258-68, 2011 Feb 25.
Article
en En
| MEDLINE
| ID: mdl-21349432
ABSTRACT
Activated mast cells trigger edema in allergic and inflammatory disease. We report a paracrine mechanism by which mast cell-released heparin increases vascular permeability in vivo. Heparin activated the protease factor XII, which initiates bradykinin formation in plasma. Targeting factor XII or kinin B2 receptors abolished heparin-triggered leukocyte-endothelium adhesion and interfered with a mast cell-driven drop in blood pressure in rodents. Intravital laser scanning microscopy and tracer measurements showed heparin-driven fluid extravasation in mouse skin microvessels. Ablation of factor XII or kinin B2 receptors abolished heparin-induced skin edema and protected mice from allergen-activated mast cell-driven leakage. In contrast, heparin and activated mast cells induced excessive edema in mice deficient in the major inhibitor of factor XII, C1 esterase inhibitor. Allergen exposure triggered edema attacks in hereditary angioedema patients, lacking C1 esterase inhibitor. The data indicate that heparin-initiated bradykinin formation plays a fundamental role in mast cell-mediated diseases.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Permeabilidad Capilar
/
Bradiquinina
/
Anafilaxis Cutánea Pasiva
/
Heparina
/
Síndrome de Fuga Capilar
/
Mastocitos
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
Immunity
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Suecia