INCREASED SULFATION OF GLYCOCONJUGATES BY CULTURED NASAL EPITHELIAL-CELLS FROM PATIENTS WITH CYSTIC-FIBROSIS
INCREASED SULFATION OF GLYCOCONJUGATES BY CULTURED NASAL EPITHELIAL-CELLS FROM PATIENTS WITH CYSTIC-FIBROSIS
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DOI：
10.1172/jci114171
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发表时间：
1989-07-01
影响因子：
15.9
通讯作者：
BOUCHER, RC
中科院分区：
文献类型：
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作者：
CHENG, PW;BOAT, TF;BOUCHER, RC
囊性纤维化（CF）呼吸道上皮表现出异常的阴离子转运，可能与肺防御异常有关。在这些研究中，我们研究了 CF 呼吸道上皮细胞的原代培养物是否异常调节参与气道粘膜防御的高分子量糖复合物 (HMG) 的硫酸盐含量。 HMG，包括自发释放到培养基中的糖胺聚糖和粘蛋白型糖蛋白以及胰蛋白酶从细胞表面释放的 HMG，用 35SO4= 和 [6-3H]-葡萄糖胺 (GlcN) 或 35SO4= 和 [3H] 丝氨酸进行代谢标记。来自 CF 细胞的所有三类 HMG 的 35S/3H 标记比率比来自正常或疾病对照细胞的 HMG 高 1.5-4 倍。 CF 细胞中 HMG 标记比率的差异被证明是 35SO4= 掺入增加的结果，而不是肽合成和释放或 HMG 糖基化减少的结果。 CF粘蛋白型HMG的浮力密度也增加，与硫酸化增加一致。这些观察结果表明，一系列 HMG 的过度硫酸化是 CF 上皮细胞的遗传决定特征，并且可能通过改变粘液分泌物的特性和/或气道表面选定细菌与 HMG 之间的相互作用而发挥重要的病理生理学作用。
Cystic fibrosis (CF) respiratory epithelial exhibit abnormal anion transport that may be linked to abnormal lung defense. In these studies, we investigated whether primary cultures of CF respiratory epithelial cells regulate abnormally the sulfate content of high molecular weight glycoconjugates (HMG) participating in airway''s mucosal defense. HMG, including glycosaminoglycans and mucin-type glycoproteins released spontaneously into medium and HMG released from cell surfaces by trypsin, were metabolically labeled with 35SO4= and [6-3H]-glucosamine (GlcN) or 35SO4= and [3H]serine. All three classes of HMG from CF cells exhibited 35S/3H labeling ratios 1.5-4-fold greater than HMG from normal or disease control cells. Differences for labeling ratios of HMG from CF cells were shown to be the consequence of increased 35SO4= incorporation rather than decreased peptide synthesis and release or HMG glycosylation. The buoyant density of CF mucin-type HMG also was increased, consistent with increased sulfation. These observations suggest that oversulfation of a spectrum of HMG is a genetically determined characteristic of CF epithelial cells and may play an important pathophysiological role by altering the properties of mucous secretions and/or the interactions between selected bacteria and HMG at the airways'' surface.