Yen A, Barrett K E, Gigli I
Department of Medicine, University of California, School of Medicine, San Diego 92103-8420.
J Invest Dermatol. 1992 Apr;98(4):488-93. doi: 10.1111/1523-1747.ep12499864.
We have previously shown that protoporphyrin (PP) plus long-wave ultraviolet light (UVA) has an inhibitory effect on the release of histamine from rat peritoneal mast cells in response to various stimuli, without compromising cell viability. In the present study, we observed that protoporphyrin at a noncytolytic dose (3 ng/ml) plus UVA irradiation (0.038 J/cm2) is also able to suppress prostaglandin D2 generation by rat peritoneal mast cells in response to calcium ionophore A23187, compound 48/80, or anti-IgE antibody by 64%, 92%, and 100%, respectively. Because of the participation of protein kinase C in stimulus-secretion coupling in mast cells, we also investigated the effect of PP plus UVA on the release of histamine induced by the protein kinase C activator, phorbol 12-myristate 13-acetate (PMA). PP plus UVA inhibited histamine release induced by PMA. The release of histamine induced by the synergistic combination of PMA (50 nM) and a low dose of calcium ionophore A23187 (0.1 microM) was also inhibited. PP plus UVA inhibited the release of histamine induced by the non-fluorescent calcium ionophore, 4-Br-A23187, by 47.8%, but had essentially no effect on changes in intracellular calcium induced by this stimulus. In contrast, both the release of histamine and changes in intracellular calcium stimulated by compound 48/80 were inhibited. We conclude from these results that PP plus UVA may affect both early and late biochemical events involved in mast cell mediator release.
我们之前已经表明，原卟啉（PP）加长波紫外线（UVA）对大鼠腹膜肥大细胞因各种刺激而释放组胺具有抑制作用，且不影响细胞活力。在本研究中，我们观察到非细胞溶解剂量（3 ng/ml）的原卟啉加UVA照射（0.038 J/cm2）也能够抑制大鼠腹膜肥大细胞因钙离子载体A23187、化合物48/80或抗IgE抗体而产生前列腺素D2，抑制率分别为64%、92%和100%。由于蛋白激酶C参与肥大细胞的刺激-分泌偶联，我们还研究了PP加UVA对蛋白激酶C激活剂佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）诱导的组胺释放的影响。PP加UVA抑制了PMA诱导的组胺释放。PMA（50 nM）与低剂量钙离子载体A23187（0.1 microM）协同组合诱导的组胺释放也受到抑制。PP加UVA抑制了非荧光钙离子载体4-Br-A23187诱导的组胺释放，抑制率为47.8%，但对该刺激诱导的细胞内钙变化基本没有影响。相比之下，化合物48/80刺激的组胺释放和细胞内钙变化均受到抑制。我们从这些结果得出结论，PP加UVA可能影响肥大细胞介质释放所涉及的早期和晚期生化事件。
