丝氨酸酯酶在肥大细胞活化中的作用。

Role of serine esterases in mast cell activation.

Khiav B E, Pearce F L

Department of Chemistry, University College London.

Br J Pharmacol. 1998 Mar;123(6):1267-73. doi: 10.1038/sj.bjp.0701724.

Abstract

A variety of chymotryptic substrates and inhibitors prevented the release of histamine and prostaglandin D2 from rat peritoneal mast cells stimulated with anti-IgE but not the calcium ionophore A23187 or a variety of polyamines. 2. The activity of the compounds was strikingly increased in cells reversibly permeabilized with ATP, indicating the importance of their effective incorporation into the cytosol. 3. The compounds produced a comparable inhibition of immunological, but not pharmacological, histamine release from human mast cells and basophils. 4. Treatment of rat mast cells with anti-IgE led to a marked increase in the total chymotryptic activity expressed by the cells. 5. Immunological, but not pharmacological, stimulation of permeabilized rat mast cells loaded with a fluorescent chymotryptic substrate led to a pronounced and rapid increase in fluorescence, indicating activation of the enzyme and hydrolysis of the substrate. These changes were attenuated by chymotryptic inhibitors. 6. In total, these data provide compelling evidence for the direct involvement of a serine protease in IgE-mediated histamine release from mast cells.

摘要

多种胰凝乳蛋白酶底物和抑制剂可阻止抗IgE刺激的大鼠腹膜肥大细胞释放组胺和前列腺素D2，但不能阻止钙离子载体A23187或多种多胺刺激下的释放。2. 在用ATP可逆性通透化的细胞中，这些化合物的活性显著增加，表明它们有效掺入胞质溶胶的重要性。3. 这些化合物对人肥大细胞和嗜碱性粒细胞的免疫性组胺释放有类似的抑制作用，但对药理学组胺释放无抑制作用。4. 用抗IgE处理大鼠肥大细胞导致细胞表达的总胰凝乳蛋白酶活性显著增加。5. 对装载有荧光胰凝乳蛋白酶底物的通透化大鼠肥大细胞进行免疫刺激而非药理学刺激，会导致荧光显著且快速增加，表明酶被激活且底物被水解。这些变化被胰凝乳蛋白酶抑制剂减弱。6. 总体而言，这些数据为丝氨酸蛋白酶直接参与肥大细胞中IgE介导的组胺释放提供了有力证据。