摘要

Chronic obstructive pulmonary disease and emphysema are a frequent result of long-term smoking, but the exact mechanisms, specifically which types of cells are associated with the lung destruction, are unclear.We studied different subsets of lymphocytes taken from portions of human lungs removed surgically to find out which lymphocytes were the most frequent, which cell-surface markers these lymphocytes expressed, and whether the lymphocytes secreted any specific factors that could be associated with disease. We found that loss of lung function in patients with chronic obstructive pulmonary disease and emphysema was associated with a high percentage of CD4+ and CD8+ T lymphocytes that expressed chemokine receptors CCR5 and CXCR3 (both markers of T helper 1 cells), but not CCR3 or CCR4 (markers of T helper 2 cells). Lung lymphocytes in patients with chronic obstructive pulmonary disease and emphysema secrete more interferon gamma--often associated with T helper 1 cells--and interferon-inducible protein 10 and monokine induced by interferon, both of which bind to CXCR3 and are involved in attracting T helper 1 cells. In response to interferon-inducible protein 10 and monokine induced by interferon, but not interferon gamma, lung macrophages secreted macrophage metalloelastase (matrix metalloproteinase-12), a potent elastin-degrading enzyme that causes tissue destruction and which has been linked to emphysema.These data suggest that Th1 lymphoctytes in the lungs of people with smoking-related damage drive progression of emphysema through CXCR3 ligands, interferon-inducible protein 10, and monokine induced by interferon.

译文

慢性阻塞性肺病和肺气肿是长期吸烟的常见结果，但是确切的机制，特别是哪些类型的细胞与肺破坏有关，还不清楚。我们研究了从手术切除的人肺部部分提取的不同淋巴细胞亚群，以找出哪些淋巴细胞最常见,这些淋巴细胞表达哪些细胞表面标记，以及淋巴细胞是否分泌任何可能与疾病相关的特定因子。我们发现，慢性阻塞性肺病和肺气肿患者的肺功能丧失与高百分比的 CD4 和 CD8 T 淋巴细胞相关，这些淋巴细胞表达趋化因子受体 CCR5 和 CXCR3 (两者都是 T helper 1 cells), 但不是 CCR3 或 CCR4 (辅助性 T 细胞 2 的标记)。慢性阻塞性肺病和肺气肿患者的肺淋巴细胞分泌更多的 γ 干扰素 -- 通常与辅助性 T 细胞 1 细胞相关 -- 以及干扰素诱导蛋白 10 和干扰素诱导的单核细胞, 两者都与 CXCR3 结合并参与吸引辅助性 T 细胞 1。响应于干扰素诱导蛋白 10 和干扰素诱导的单核细胞，而不是干扰素 γ，肺巨噬细胞分泌巨噬细胞金属弹性蛋白酶 (基质 metalloproteinase-12),一种有效的弹性蛋白降解酶，可导致组织破坏，并与肺气肿有关。这些数据表明，吸烟相关损伤患者肺部的 Th1 淋巴细胞通过 CXCR3 配体、干扰素诱导蛋白 10 和干扰素诱导的单核细胞推动肺气肿的进展。