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Induction of mast cell accumulation by chymase via an enzymatic activity- and intercellular adhesion molecule-1-dependent mechanism.
Zhang, Huiyun; Wang, Junling; Wang, Ling; Zhan, Mengmeng; Li, Shigang; Fang, Zeman; Xu, Ciyan; Zheng, Yanshan; He, Shaoheng.
Afiliación
  • Zhang H; Translational Medicine Institute, Shenyang Medical College, Shenyang, Liaoning, China.
  • Wang J; Allergy and Clinical Immunology Research Centre, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China.
  • Wang L; Translational Medicine Institute, Shenyang Medical College, Shenyang, Liaoning, China.
  • Zhan M; Allergy and Clinical Immunology Research Centre, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China.
  • Li S; Translational Medicine Institute, Shenyang Medical College, Shenyang, Liaoning, China.
  • Fang Z; Medical School, China Three Gorges University, Yichang, Hubei, China.
  • Xu C; Allergy and Inflammation Research Institute, Shantou University Medical College, Shantou, China.
  • Zheng Y; Allergy and Inflammation Research Institute, Shantou University Medical College, Shantou, China.
  • He S; Allergy and Inflammation Research Institute, Shantou University Medical College, Shantou, China.
Br J Pharmacol ; 175(4): 678-692, 2018 02.
Article en En | MEDLINE | ID: mdl-29197072
BACKGROUND AND PURPOSE: Chymase is a unique, abundant secretory product of mast cells and a potent chemoattractant for eosinophils, monocytes and neutrophils, but little is known of its influence on mast cell accumulation. EXPERIMENTAL APPROACH: A mouse peritoneal inflammation model, cell migration assay and flowcytometry analysis, were used to investigate the role of chymase in recruiting mast cells. KEY RESULTS: Chymase increased, by up to 5.4-fold, mast cell numbers in mouse peritoneum. Inhibitors of chymase, heat-inactivation of the enzyme, sodium cromoglycate and terfenadine, and pretreatment of mice with anti-intercellular adhesion molecule 1, anti-L-selectin, anti-CD11a and anti-CD18 antibodies dramatically diminished the chymase-induced increase in mast cell accumulation. These findings indicate that this effect of chymase is dependent on its enzymatic activity and activation of adhesion molecules. In addition, chymase provoked a significant increase in 5-HT and eotaxin release (up to 1.8- and 2.2-fold, respectively) in mouse peritoneum. Since 5-HT, eotaxin and RANTES can induce marked mast cell accumulation, these indirect mechanisms may also contribute to chymase-induced mast cell accumulation. Moreover, chymase increased the trans-endothelium migration of mast cells in vitro indicating it also acts as a chemoattractant. CONCLUSION AND IMPLICATIONS: The finding that mast cells accumulate in response to chymase implies further that chymase is a major pro-inflammatory mediator of mast cells. This effect of chymase, a major product of mast cell granules, suggests a novel self-amplification mechanism for mast cell accumulation in allergic inflammation. Mast cell stabilizers and inhibitors of chymase may have potential as a treatment of allergic disorders.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Movimiento Celular / Molécula 1 de Adhesión Intercelular / Quimasas / Mastocitos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Br J Pharmacol Año: 2018 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Movimiento Celular / Molécula 1 de Adhesión Intercelular / Quimasas / Mastocitos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Br J Pharmacol Año: 2018 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido