HISTAMINE MODULATION T-CELL IMMOBILIZATION IN THE LUNG

肺部的某些炎症反应的特征是 淋巴细胞占优势，但效应器的作用机制 淋巴细胞被招募到炎症部位还不是很清楚。 单核细胞和中性粒细胞可以通过产生和 趋化因子和迁移抑制因子的相互作用。 我们实验室的研究最近阐明了一个类似的系统 对人T淋巴细胞--淋巴细胞趋化因子(LCF)和两种 非细胞毒性淋巴细胞迁移抑制因子(LyMIF75K和 携带组胺受体的人血T淋巴细胞产生LyMIF35K) 作为对组胺的反应，组胺是组织肥大细胞和 嗜碱性细胞。抑制迁移的机制(S)是 不知道，尽管有证据表明至少有一位LyMIF (LyMIF35K)通过一种特定的细胞膜受体发挥作用。 LyMIF对淋巴细胞代谢或细胞骨架的影响 可移动的、功能尚不清楚。我提议调查 LyMIF75K的来源、理化特性及生物活性 和LyMIF35K。利用标准分离技术，由 人类血淋巴细胞和T-T杂交瘤将被提纯到 同质性。使用提纯的材料，我将调查 淋巴细胞亚群上的这些淋巴因子。放射性标记的LyMIF将是 生产的，这种材料用于研究LyMIF细胞膜 受体相互作用。选择性激活居留或渗入 携带组胺受体的T淋巴细胞产生LCF和LyMIF可能 解释效应器淋巴细胞的募集和固定 肺部的炎症部位。对变量的理解 可能会影响LyMIF的产生和对靶T淋巴细胞的作用 某些淋巴细胞介导的炎性肺的新治疗方法 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.