Nakata J, Tamaoki J, Takeyama K, Takeda Y, Yamawaki I, Kondo M, Nagai A
First Department of Medicine, Tokyo Women's Medical College, Japan.
Nihon Kokyuki Gakkai Zasshi. 1998 Oct;36(10):845-50.
Heparin and related proteoglycans are released from mast cells and possess anti-inflammatory and anti-complement activities. To elucidate whether heparin affects goblet cell secretion in asthmatic airways and, if so, what the mechanism of action is, we studied guinea pigs sensitized with ovalbumin (OVA) by determining the mucus score (MS) of tracheal goblet cells stained with Alcian blue and PAS. Inhalation of OVA caused a rapid decrease in MS in a dose-dependent manner, with the maximal decrease being from 545 +/- 26 to 192 +/- 35 (p < 0.001), indicating an increase in goblet cell mucus discharge. This effect was selectively inhibited by the histamine H2 receptor blockade with cimetidine. Prior inhalation of heparin inhibited OVA-induced goblet cell secretion in a dose-dependent fashion, but had no effect on histamine-induced goblet cell secretion. The OVA-induced histamine release from the tracheal tissue was likewise inhibited by heparin. These results suggest that allergic challenge stimulates airway goblet cell secretion mainly through the release of histamine and the concomitant activation of histamine H2 receptors on goblet cells, and that heparin protects against this effect by inhibiting the histamine release from mast cells.
肝素及相关蛋白聚糖由肥大细胞释放,具有抗炎和抗补体活性。为了阐明肝素是否影响哮喘气道中杯状细胞的分泌,如果是,其作用机制是什么,我们通过测定用阿尔辛蓝和PAS染色的气管杯状细胞的黏液评分(MS),研究了用卵清蛋白(OVA)致敏的豚鼠。吸入OVA导致MS迅速呈剂量依赖性下降,最大降幅从545±26降至192±35(p<0.001),表明杯状细胞黏液分泌增加。西咪替丁对组胺H2受体的阻断选择性地抑制了这种作用。预先吸入肝素以剂量依赖性方式抑制OVA诱导的杯状细胞分泌,但对组胺诱导的杯状细胞分泌无影响。肝素同样抑制OVA诱导的气管组织组胺释放。这些结果表明,变应原激发主要通过组胺释放和随之而来的杯状细胞上组胺H2受体的激活来刺激气道杯状细胞分泌,并且肝素通过抑制肥大细胞组胺释放来预防这种作用。