Leukocytic cell sources of airway tissue kallikrein
Leukocytic cell sources of airway tissue kallikrein
复制标题
DOI：
10.1152/ajplung.00129.2003
复制
发表时间：
2004-04-01
影响因子：
4.9
通讯作者：
Abraham, WM
中科院分区：
文献类型：
--
作者：
Lauredo, IT;Forteza, RM;Abraham, WM
肺组织激肽释放酶(TK)是一种丝氨酸蛋白酶，通过产生激动素和缓激肽在哮喘的病理生理学中发挥作用，这两种介质有助于气道高反应性。在以前的研究中，我们观察到过敏性绵羊在呼吸道变应原攻击后，支气管肺泡灌洗液中TK活性的双相增加。虽然腺体TK可能是最初TK增加的主要来源，但与气道高反应性发展相关的晚期TK增加的来源可能依赖于激活的驻留和招募的炎症细胞，包括肺泡巨噬细胞(AM)和中性粒细胞(PMN)。这些细胞随着TK活性的后期增加而增加。为了验证这一假设，我们从支气管肺泡灌洗液中获得AM，从绵羊血液中获得PMN和单核细胞(AM的前体)，并确定这些细胞是否含有TK，以及这些细胞在激活时是否可以释放TK。利用共聚焦显微镜、免疫细胞化学技术和酶活性分析，我们发现所有三种类型的细胞都含有和分泌TK。3种细胞均表现出TK的基础释放，酵母多糖刺激后TK释放增加。此外，在佛波酯存在的情况下，PMN还释放TK，这表明这些细胞有多种分泌途径。此外，我们还发现人类单核细胞也含有和分泌TK。我们得出结论，在呼吸道中，单核细胞、中性粒细胞和AM可能参与了TK活性的增加。了解呼吸道中TK的来源对于了解炎症机制可能是重要的，这些炎症机制有助于哮喘的病理生理机制，并可能有助于开发新的治疗方法来控制疾病。
Lung tissue kallikrein (TK) is a serine proteinase that putatively plays a role in the pathophysiology of asthma by generating kallidin and bradykinin, mediators that contribute to airway hyperresponsiveness. In previous studies we observed biphasic increases in TK activity in bronchoalveolar lavage fluid following airway allergen challenge in allergic sheep. Although glandular TK is likely a major source of the initial increase in TK, the sources of the late increases in TK that are associated with the development of airway hyperresponsiveness may be dependent on activated resident and recruited inflammatory cells including alveolar macrophages (AMs) and neutrophils (PMNs). These cells increase concomitantly with the late increases in TK activity. To test this hypothesis, we obtained AMs from bronchoalveolar lavage fluid and PMNs and monocytes ( precursors of AMs) from sheep blood and determined whether these cells contained TK and whether these same cells could release TK upon activation. Using confocal microscopy, immunocytochemical techniques, and enzyme activity assays, we found that all three cell types contained and secreted TK. All three cell types demonstrated basal release of TK, which could be increased after stimulation with zymosan. In addition, PMNs also released TK in the presence of phorbol ester, suggesting multiple secretory pathways in these cells. Furthermore, we showed that human monocytes also contain and secrete TK. We conclude that in the airways, monocytes, PMNs, and AMs may contribute to increased TK activity. Knowing the sources of TK in the airways could be important in understanding the mechanisms of inflammation that contribute to the pathophysiology of asthma and may help in the development of new therapies to control the disease.