Acid and base secretion in the Calu-3 model of human serous cells
Acid and base secretion in the Calu-3 model of human serous cells
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DOI：
10.1152/ajplung.00036.2004
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发表时间：
2004-12-01
影响因子：
4.9
通讯作者：
Wine, JJ
中科院分区：
文献类型：
--
作者：
Krouse, ME;Talbott, JF;Wine, JJ
粘膜下腺是呼吸道粘液的主要来源，而呼吸道粘液是肺固有防御的重要组成部分。囊性纤维化患者的气道腺有缺陷，表现为完全不分泌血管活性肠肽或Forsklin，后者会增加细胞内cAMP浓度。这种缺陷归因于腺浆细胞，它们表达囊性纤维化跨膜电导调节因子。CALU-3细胞模拟浆液性细胞的许多特征，分泌Cl-和HCO3-，其中HCO3-分泌主要用于Forsklin刺激，而Cl-分泌主要用于打开基底外侧K+通道以使细胞超极化。我们用pH恒定和离子置换实验来阐明这两种分泌模式的机制和后果。我们证实，CALU-3细胞主要分泌HCO3-以响应Forsklin。出乎意料的是，在K+通道开放剂的作用下，HCO3-的分泌仍在继续，同时增加了Cl-的分泌。超极化细胞分泌HCO3-是通过二氧化碳转化为HCO3-实现的，与乙酰唑胺类似，HCO3-的分泌减少了50%。在所有实验中都观察到了碱基等效电流和短路电流之间的差距，并可追溯到通过哇巴因敏感的K+依赖过程(可能是H+-K+-ATPase)分泌H+，该过程部分中和了分泌的HCO3-。HCO3-和H+的联合分泌可能有助于解释这一令人费解的发现，即从正常和CF腺体分泌的粘液与从Forsklin或ACh刺激的腺体分泌的粘液具有相同的酸性pH。这也有助于解释人类呼吸道腺体是如何产生低张粘液的。
Submucosal glands are the primary source of airway mucus, a critical component of lung innate defenses. Airway glands are defective in cystic fibrosis (CF), showing a complete absence of secretion to vasoactive intestinal peptide or forskolin, which increase intracellular cAMP concentration. This defect is attributed to gland serous cells, which express the cystic fibrosis transmembrane conductance regulator. Calu-3 cells, which mimic many features of serous cells, secrete Cl- and HCO3-, with HCO3- secretion predominating for forskolin stimulation and Cl- secretion predominating for stimuli that open basolateral K+ channels to hyperpolarize the cells. We used pH stat and ion substitution experiments to clarify the mechanisms and consequences of these two modes of secretion. We confirm that Calu-3 cells secrete primarily HCO3- in response to forskolin. Unexpectedly, HCO3- secretion continued in response to K+ channel openers, with Cl- secretion being added to it. Secretion of HCO3- from hyperpolarized cells occurs via the conversion of CO2 to HCO3- and is reduced by similar to50% with acetazolamide. A gap between the base equivalent current and short-circuit current was observed in all experiments and was traced to secretion of H+ via a ouabain-sensitive, K+-dependent process (possibly H+-K+-ATPase), which partially neutralized the secreted HCO3-. The conjoint secretion of HCO3- and H+ may help explain the puzzling finding that mucus secreted from normal and CF glands has the same acidic pH as does mucus from glands stimulated with forskolin or ACh. It may also help explain how human airway glands produce mucus that is hypotonic.