de Paulis A, Ciccarelli A, Marinò I, de Crescenzo G, Marinò D, Marone G
School of Medicine, University of Naples Federico II, Italy.
Arthritis Rheum. 1997 Mar;40(3):469-78. doi: 10.1002/art.1780400313.
To evaluate the in vitro effects of 4 antiinflammatory and 5 immunosuppressive agents on the release of preformed and de novo-synthesized mediators from human synovial mast cells (HSyMC) activated by immunologic and nonimmunologic stimuli.
The effects of antiinflammatory and immunosuppressive agents were evaluated on the in vitro release of histamine and tryptase and the de novo synthesis of prostaglandin D2 (PGD2) and leukotriene C4 (LTC4) by HSyMC challenged with anti-IgE and substance P.
Nimesulide, a sulfonanilide nonsteroidal antiinflammatory drug (NSAID) chemically unrelated to other acidic NSAIDs (such as acetylsalicylic acid [ASA], diclofenac, and piroxicam) inhibited in a concentration-dependent manner the release of preformed (histamine and tryptase) mediators from HSyMC challenged with anti-IgE. In contrast, diclofenac and piroxicam had little or no effect on HSyMC activated by anti-IgE. ASA, diclofenac, piroxicam, and nimesulide caused a concentration-dependent inhibition of IgE-mediated PGD2 release from HSyMC. Nimesulide, but not diclofenac or piroxicam, also inhibited the de novo synthesis of LTC4 by HSyMC challenged with anti-IgE. Nimesulide, diclofenac, and piroxicam had no effect on HSyMC activated by substance P. Cyclosporin A (CSA) inhibited histamine release from HSyMC challenged with anti-IgE, whereas cyclosporin H (CSH) had no effect. FK-506 also inhibited histamine release from HSyMC activated by anti-IgE, whereas rapamycin had no effect. Neither CSA, CSH, FK-506, nor rapamycin inhibited the release of histamine from HSyMC induced by substance P. Methotrexate had no effect on the release of mediators from these cells, whereas adenosine (R-phenylisopropyl adenosine and 5'-N-ethylcarboxamide adenosine) enhanced histamine release from immunologically activated HSyMC in a concentration-dependent manner.
Mast cells isolated from human synovia display 4 levels of pharmacologic heterogeneity with regard to 1) the inhibitory effects of 4 antiinflammatory drugs; 2) the capacity of different immunosuppressive drugs to exert antiinflammatory activity; 3) the inhibition of the release of different mediators; and 4) the capacity of antiinflammatory and immunosuppressive drugs to modulate HSyMC activated by different stimuli. This complexity of pharmacologic modulation of HSyMC in vitro might help explain the different activity of the compounds used to treat various pathophysiologic aspects of the inflammatory arthritides.
评估4种抗炎药和5种免疫抑制剂对免疫和非免疫刺激激活的人滑膜肥大细胞（HSyMC）中预先形成的和新合成的介质释放的体外作用。
评估抗炎药和免疫抑制剂对HSyMC经抗IgE和P物质刺激后组胺和类胰蛋白酶的体外释放以及前列腺素D2（PGD2）和白三烯C4（LTC4）的新合成的影响。
尼美舒利，一种与其他酸性非甾体抗炎药（如阿司匹林[ASA]、双氯芬酸和吡罗昔康）化学结构无关的磺酰苯胺类非甾体抗炎药（NSAID），以浓度依赖性方式抑制抗IgE刺激的HSyMC中预先形成的（组胺和类胰蛋白酶）介质的释放。相比之下，双氯芬酸和吡罗昔康对抗IgE激活的HSyMC几乎没有影响。ASA、双氯芬酸、吡罗昔康和尼美舒利对HSyMC中IgE介导的PGD2释放产生浓度依赖性抑制。尼美舒利，但不是双氯芬酸或吡罗昔康，也抑制抗IgE刺激HSyMC中LTC4的新合成。尼美舒利、双氯芬酸和吡罗昔康对P物质激活的HSyMC没有影响。环孢素A（CSA）抑制抗IgE刺激的HSyMC中组胺的释放，而环孢素H（CSH）没有影响。FK-506也抑制抗IgE激活的HSyMC中组胺的释放，而雷帕霉素没有影响。CSA、CSH、FK-506和雷帕霉素均未抑制P物质诱导的HSyMC中组胺的释放。甲氨蝶呤对这些细胞中介质的释放没有影响，而腺苷（R-苯异丙基腺苷和5'-N-乙基羧酰胺腺苷）以浓度依赖性方式增强免疫激活的HSyMC中组胺的释放。
从人滑膜分离的肥大细胞在以下方面表现出4个药理学异质性水平：1）4种抗炎药的抑制作用；2）不同免疫抑制剂发挥抗炎活性的能力；3）对不同介质释放的抑制；4）抗炎药和免疫抑制剂调节不同刺激激活的HSyMC的能力。HSyMC体外药理学调节的这种复杂性可能有助于解释用于治疗炎性关节炎各种病理生理方面的化合物的不同活性。
Zotero 插件