Hogaboam C M, Befus A D, Wallace J L
Gastrointestinal Research Group, Faculty of Medicine, University of Calgary, Alberta, Canada.
J Immunol. 1993 Oct 1;151(7):3767-74.
Release of inflammatory mediators by mast cells can be modulated by certain cytokines and by nitric oxide. An in vitro platelet aggregation bioassay was used to assess the effects of interleukin-1 beta (IL-1 beta) on the release of platelet-activating factor and nitric oxide from resting or ionophore-activated peritoneal mast cells (PMC) from rat. PMC spontaneously released a substance that inhibits thrombin-stimulated platelet aggregation. The activity of this substance is abolished by addition of hemoglobin to the platelet suspension and augmented by preincubation of the PMC with L-arginine, suggesting that it is nitric oxide. Within minutes, IL-1 beta concentration-dependently (1 pg/ml-100 ng/ml) enhanced the release from activated PMC of nitric oxide, as measured by its ability to inhibit thrombin-induced platelet aggregation, and as confirmed with a biochemical assay for nitrite. This action of IL-1 beta was inhibited by pretreatment of PMC with a calmodulin antagonist (calmidazolium), an IL-1 receptor antagonist, or either of two nitric oxide synthase inhibitors (L-NAME and LY-83583). IL-1 beta also inhibited the release of platelet-activating factor from PMC through a nitric-oxide-dependent mechanism. These results demonstrate that IL-1 beta is a potent and rapid-acting modulator of mast cell reactivity, stimulating nitric oxide release while inhibiting the production of platelet-activating factor.
肥大细胞释放炎症介质可受到某些细胞因子和一氧化氮的调节。采用体外血小板聚集生物测定法评估白细胞介素-1β（IL-1β）对大鼠静息或经离子载体激活的腹腔肥大细胞（PMC）释放血小板活化因子和一氧化氮的影响。PMC自发释放一种抑制凝血酶刺激的血小板聚集的物质。向血小板悬液中加入血红蛋白可消除该物质的活性，而用L-精氨酸预孵育PMC可增强其活性，提示该物质为一氧化氮。数分钟内，IL-1β以浓度依赖性方式（1 pg/ml - 100 ng/ml）增强激活的PMC释放一氧化氮，这通过其抑制凝血酶诱导的血小板聚集的能力来测定，并经亚硝酸盐生化测定证实。用钙调蛋白拮抗剂（氯咪唑）、IL-1受体拮抗剂或两种一氧化氮合酶抑制剂（L-NAME和LY-83583）之一预处理PMC可抑制IL-1β的这一作用。IL-1β还通过一氧化氮依赖性机制抑制PMC释放血小板活化因子。这些结果表明，IL-1β是肥大细胞反应性的一种强效且快速起作用的调节剂，刺激一氧化氮释放同时抑制血小板活化因子的产生。
