Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia.
Allergy. 2011 Sep;66(9):1231-41. doi: 10.1111/j.1398-9995.2011.02616.x. Epub 2011 May 10.
Activated mast cell densities are increased on the airway smooth muscle in asthma where they may modulate muscle functions and thus contribute to airway inflammation, remodelling and airflow obstruction.
To determine the effects of human lung mast cells on the secretory and proliferative functions of airway smooth muscle cells from donors with and without asthma.
Freshly isolated human lung mast cells were stimulated with IgE/anti-IgE. Culture supernatants were collected after 2 and 24 h and the mast cells lysed. The supernatants/lysates were added to serum-deprived, subconfluent airway smooth muscle cells for up to 48 h. Released chemokines and extracellular matrix were measured by ELISA, proliferation was quantified by [(3) H]-thymidine incorporation and cell counting, and intracellular signalling by phospho-arrays.
Mast cell 2-h supernatants reduced CCL11 and increased CXCL8 and fibronectin production from both asthmatic and nonasthmatic muscle cells. Leupeptin reversed these effects. Mast cell 24-h supernatants and lysates reduced CCL11 release from both muscle cell types but increased CXCL8 release by nonasthmatic cells. The 24-h supernatants also reduced asthmatic, but not nonasthmatic, muscle cell DNA synthesis and asthmatic cell numbers over 5 days through inhibiting extracellular signal-regulated kinase (ERK) and phosphatidylinositol (PI3)-kinase pathways. However, prostaglandins, thromboxanes, IL-4 and IL-13 were not involved in reducing the proliferation.
Mast cell proteases and newly synthesized products differentially modulated the secretory and proliferative functions of airway smooth muscle cells from donors with and without asthma. Thus, mast cells may modulate their own recruitment and airway smooth muscle functions locally in asthma.
在哮喘的气道平滑肌中，激活的肥大细胞密度增加，它们可能调节肌肉功能，从而促进气道炎症、重塑和气流阻塞。
确定人肺肥大细胞对来自哮喘和非哮喘供体的气道平滑肌细胞的分泌和增殖功能的影响。
用 IgE/抗 IgE 刺激新鲜分离的人肺肥大细胞。在 2 小时和 24 小时后收集培养上清液，并裂解肥大细胞。将上清液/裂解物添加到血清剥夺的、亚汇合的气道平滑肌细胞中，持续长达 48 小时。通过 ELISA 测量释放的趋化因子和细胞外基质，通过 [(3) H]-胸苷掺入和细胞计数定量增殖，通过磷酸化阵列测量细胞内信号转导。
肥大细胞 2 小时的上清液减少了 CCL11 的产生，并增加了来自哮喘和非哮喘肌肉细胞的 CXCL8 和纤维连接蛋白的产生。亮肽素逆转了这些作用。肥大细胞 24 小时的上清液和裂解物减少了两种肌肉细胞类型的 CCL11 释放，但增加了非哮喘细胞的 CXCL8 释放。24 小时的上清液还通过抑制细胞外信号调节激酶 (ERK) 和磷脂酰肌醇 (PI3)-激酶途径，减少了 5 天内哮喘和非哮喘肌肉细胞的 DNA 合成和哮喘细胞的数量。然而，前列腺素、血栓素、IL-4 和 IL-13 不参与抑制增殖。
肥大细胞蛋白酶和新合成的产物可调节来自哮喘和非哮喘供体的气道平滑肌细胞的分泌和增殖功能。因此，肥大细胞可能在哮喘中局部调节其自身的募集和气道平滑肌功能。
