Allen-Gipson D S, Chen M, Heiman A S
College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, 32307, USA.
Proc Soc Exp Biol Med. 1998 Apr;217(4):439-44. doi: 10.3181/00379727-217-44254.
Mast cells are effectors of inflammatory responses. When triggered by immunological or nonimmunological mechanisms, mast cells release potent biological mediators from preformed stores and synthesize others de novo. In previous investigations from this laboratory, the signal transduction pathways of cloned 10P2 cytokine-independent mast cells were explored. Results suggested that 10P2 cells undergo activation-secretion coupling assessed as release of stored [14C]serotonin (5-HT) when challenged with IgE-specific antigen, influx of extracellular calcium, release of intracellular calcium stores, or by direct activation of protein kinase C isozymes. In the present investigations, cytokine proliferative effects and modulatory roles on release of stored [14C]5-HT have been explored. Following passive sensitization with anti-dinitrophenol (anti-DNP) IgE and challenge with DNP, mast cells released up to 32% of the stored [14C]5-HT. Pretreatment of cells with 10, 30, or 50 ng/ml stem cell factor (SCF) did not alter the response. SCF did not directly induce [14C]5-HT release. Pretreatment with 25 ng/ml interleukin-9 (IL-9) significantly potentiated the IgE-antigen release by 51.1%, 35.7%, or 31.6% when challenged with 3, 10 or 30 ng/ml DNP-HSA. Treatment of cells with 1-100 ng/ml SCF for 72 hr resulted in significantly enhanced proliferation whereas this did not occur when cells were treated with 1-100 ng/ml IL-9. Collectively, these results suggest that SCF alone has a proliferative effect, does not alter the IgE-specific antigen signal transduction pathway, and does not directly stimulate mast cell degranulation. In contrast, IL-9 potentiates the IgE-antigen signal transduction response but exerts no proliferative response. Reports of effects of orally administered cytokines are now beginning to emerge. This raises the possibility that cytokines may be a future therapeutic approach to treatment of allergic and nonallergic inflammatory diseases. The 10P2 cytokine-independent mast cell line may be a valuable adjunct to existing mast cell models as this avenue of drug discovery is explored.
肥大细胞是炎症反应的效应细胞。当受到免疫或非免疫机制触发时，肥大细胞会从预先形成的储存库中释放强效生物介质，并重新合成其他介质。在本实验室之前的研究中，对克隆的10P2细胞因子非依赖性肥大细胞的信号转导途径进行了探索。结果表明，当用IgE特异性抗原、细胞外钙内流、细胞内钙储存释放或通过直接激活蛋白激酶C同工酶进行刺激时，10P2细胞会发生激活-分泌偶联，表现为储存的[14C]血清素（5-羟色胺，5-HT）释放。在本研究中，探讨了细胞因子对储存的[14C]5-HT释放的增殖作用和调节作用。用抗二硝基苯酚（抗-DNP）IgE进行被动致敏并以DNP刺激后，肥大细胞释放了高达32%的储存[14C]5-HT。用10、30或50 ng/ml干细胞因子（SCF）对细胞进行预处理并未改变该反应。SCF未直接诱导[14C]5-HT释放。用25 ng/ml白细胞介素-9（IL-9）预处理，当用3、10或30 ng/ml二硝基苯酚-人血清白蛋白（DNP-HSA）刺激时，IgE-抗原释放分别显著增强了51.1%、35.7%或31.6%。用1-100 ng/ml SCF处理细胞72小时导致增殖显著增强，而用1-100 ng/ml IL-9处理细胞时则未出现这种情况。总体而言，这些结果表明，单独的SCF具有增殖作用，不改变IgE特异性抗原信号转导途径，也不直接刺激肥大细胞脱颗粒。相比之下，IL-9增强了IgE-抗原信号转导反应，但不产生增殖反应。口服细胞因子作用的报道现在开始出现。这增加了细胞因子可能成为未来治疗过敏性和非过敏性炎症性疾病的一种治疗方法的可能性。随着探索这条药物发现途径，10P2细胞因子非依赖性肥大细胞系可能成为现有肥大细胞模型的有价值辅助工具。
