HISTAMINE MODULATION T-CELL IMMOBILIZATION IN THE LUNG

肺中的某些炎症反应的特征在于 淋巴细胞的优势，但效应器 淋巴细胞被募集到炎症部位的原因还不清楚。 单核细胞和嗜中性粒细胞可以通过产生和 趋化因子和迁移抑制性淋巴因子相互作用。 我们实验室的研究最近阐明了一个类似的系统 人T淋巴细胞-淋巴细胞趋化因子（LCF）和两个 非细胞毒性淋巴细胞迁移抑制因子（LyMIF 75 K和 由携带组胺受体的人血T淋巴细胞产生的LyMIF 35 K 组胺是组织肥大细胞血管活性产物， 嗜碱性粒细胞 实现迁移抑制的机制是 不知道，虽然有证据表明，至少有一个LyMIFs LyMIF 35 K通过一种特异性细胞膜受体发挥作用。 LyMIFs对淋巴细胞代谢或细胞骨架的影响， 能动性，功能尚不清楚。 我提议调查 LyMIF 75 K的来源、理化性质及生物活性 LyMIF35K 利用标准分离技术， 将纯化人血淋巴细胞和T-T杂交瘤， 同质性 使用纯化的材料，我将研究 这些淋巴因子对淋巴细胞亚群的影响。 放射性标记的LyMIFs将 生产，这种材料用于研究LyMIF细胞膜 受体相互作用 选择性激活常驻或浸润 产生LCF和LyMIFs的携带组胺受体的T淋巴细胞可以 解释效应淋巴细胞的募集和固定， 肺部的炎症部位 对变量的理解 影响LyMIF的产生和对靶T淋巴细胞的作用可能导致 在一些淋巴细胞介导的炎症性肺的新治疗方法中， 疾病

Certain inflammatory reactions in the lung are characterized by a predominance of lymphocytes, yet the mechanism by which effector lymphocytes are recruited to sites of inflammation is not well understood. Monocytes and neutrophils can be recruited through the production and interaction of chemoattractant and migration inhibitory lymphokines. Studies from our laboratory have recently elucidated an analogous system for human T lymphocytes - a lymphocyte chemokinetic factor (LCF) and two non-cytotoxic lymphocyte migration inhibitory factors (LyMIF75K and LyMIF35K) produced by histamine receptor-bearing human blood T lymphocytes in response to histamine, a vasoactive product of tissue mast cells and basophils. The mechanism(s) by which migration inhibition is effected is not known, though there is evidence that at least one of the LyMIFs (LyMIF35K) works through the medium of a specific cell-membrane receptor. The effect of LyMIFs on lymphocyte metabolic or cytoskeletal, and thus motile, function is not yet known. I propose to investigate the cell of origin, physicochemical characteristics and biologic activity of LyMIF75K and LyMIF35K. Utilizing standard separation techniques, LyMIFs produced by human blood lymphocytes and T-T hybridomas will be purified to homogeneity. Using purified material, I will investigate the effect of these lymphokines on lymphocyte subsets. Radiolabeled LyMIFs will be produced, and this material used to investigate LyMIF-cell membrane receptor interactions. Selective activation of resident or infiltrating histamine receptor-bearing T lymphocytes to produce LCF and LyMIFs may explain the recruitment and immobilization of effector lymphocytes to inflammatory sites in the lung. An understanding of the variables affecting LyMIF production and actions on target T lymphocytes may result in new approaches to therapy of some lymphocyte-mediated inflammatory lung diseases.