Huiyun Zhang1,2, Junling Wang1, Ling Wang2, Mengmeng Zhan1, Shigang Li3, Zeman Fang4, Ciyan Xu4, Yanshan Zheng4, Shaoheng He1,2. 1. Translational Medicine Institute, Shenyang Medical College, Shenyang, Liaoning, China. 2. Allergy and Clinical Immunology Research Centre, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China. 3. Medical School, China Three Gorges University, Yichang, Hubei, China. 4. Allergy and Inflammation Research Institute, Shantou University Medical College, Shantou, China.
Abstract
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.
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.
Authors: Shaoheng He; H Zhang; H Chen; H Yang; T Huang; Y Chen; J Lin; F Wang; X Chen; T-L Li; Pingchang Yang Journal: Allergy Date: 2010-03-20 Impact factor: 13.146
Authors: Manne Krop; Zeynep G Ozünal; Wenxia Chai; René de Vries; Durk Fekkes; Angelique M Bouhuizen; Ingrid M Garrelds; A H Jan Danser Journal: Eur J Pharmacol Date: 2010-05-10 Impact factor: 4.432
Authors: Giorgio Ciprandi; Maria Angela Tosca; Cristina Cosentino; Anna Maria Riccio; Giovanni Passalacqua; Giorgio Walter Canonica Journal: J Allergy Clin Immunol Date: 2003-10 Impact factor: 10.793