Hyporesponsiveness of canine bronchoalveolar lymphocytes to mitogens: inhibition of lymphocyte proliferation by alveolar macrophages.
Hyporesponsiveness of canine bronchoalveolar lymphocytes to mitogens: inhibition of lymphocyte proliferation by alveolar macrophages.
复制标题
犬支气管肺泡淋巴细胞对有丝分裂原的低反应性：肺泡巨噬细胞抑制淋巴细胞增殖。
DOI：
10.4049/jimmunol.122.2.542
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发表时间：
1979
影响因子：
4.4
通讯作者：
F. Herskowitz
中科院分区：
文献类型：
--
作者：
M. Ansfield;H. B. Kaltreider;J. Caldwell;F. Herskowitz
经灌洗分离的犬支气管肺泡细胞(65%巨噬细胞、26%淋巴细胞和9%粒细胞)对刀豆蛋白A、植物血凝素或商陆有丝分裂原刺激反应明显减弱。探讨了支气管肺泡淋巴细胞缺乏反应性的机制。通过顺序吸附塑料(非贴壁细胞)和尼龙羊毛过滤(柱纯化细胞)，去除未分离的支气管肺泡细胞的贴壁细胞。未贴壁和柱状纯化的细胞大量去除巨噬细胞，富含淋巴细胞，对有丝分裂原的反应显著增加(最高可达7倍)。
未分离的支气管肺泡细胞的制备明显抑制血淋巴细胞对有丝分裂原的反应；未贴壁和柱纯化的细胞表现出最小的抑制活性。由未分离的支气管肺泡细胞制备的塑料贴壁细胞含有高达93%的巨噬细胞，这些贴壁细胞与血淋巴细胞共同培养时，是有丝分裂原反应的有力抑制者。贴壁细胞的抑制活性是抗辐射的，加入低浓度的吲哚美辛可逆转这一抑制活性。这些数据表明，肺泡巨噬细胞是负责这种抑制活性的贴壁细胞。
非粘附性和柱状纯化的支气管肺泡淋巴细胞的反应性虽然显著高于同等数量的未分离的支气管肺泡淋巴细胞，但始终低于类似制备的血液淋巴细胞的反应性的25%。血液和肺淋巴细胞之间的细胞活力没有发现差异。无论是添加消炎痛，还是添加丝裂霉素处理的血液单个核细胞，都不会增加柱状纯化的支气管肺泡淋巴细胞的反应。
我们的研究证明了两种限制犬肺淋巴细胞对有丝分裂刺激的反应的机制：肺泡巨噬细胞抑制淋巴细胞增殖和支气管肺泡淋巴细胞固有的低反应性。这些在调节肺对吸入性抗原的反应方面可能是重要的。
Unfractionated canine bronchoalveolar cells (65% macrophages, 26% lymphocytes, and 9% granulocytes) obtained by lavage were markedly hyporesponsive to stimulation with concanavalin A, phytohemagglutinin, or pokeweed mitogen. The mechanisms responsible for the lack of responsiveness of bronchoalveolar lymphocytes were investigated. Unfractionated bronchoalveolar cells were depleted of adherent cells by sequential adsorption on plastic (nonadherent cells) and by nylon wool filtration (column-purified cells). Nonadherent and column-purified cells were substantially depleted of macrophages, enriched for lymphocytes, and displayed marked increases in their responses to mitogens (up to 7-fold).
Preparations of unfractionated bronchoalveolar cells markedly suppressed the responses of blood lymphocytes to mitogens; nonadherent and column-purified cells displayed minimal suppressive activity. Plastic-adherent cells, prepared from unfractionated bronchoalveolar cells, contained up to 93% macrophages and these adherent cells were potent suppressors of mitogen-responses when co-cultured with blood lymphocytes. Suppressor activity of adherent cells was radioresistant and was reversed by the addition to cultures of low concentrations of indomethacin. The data indicate that alveolar macrophages are the adherent cells responsible for this suppressor activity.
The responses of nonadherent and column-purified bronchoalveolar lymphocytes, although substantially greater than those of equal numbers of unfractionated bronchoalveolar lymphocytes, were consistently less than 25% of the responses of similarly prepared blood lymphocytes. Differences in cell viability between blood and lung lymphocytes were not found. Neither the addition of indomethacin nor the addition of mitomycintreated blood mononuclear cells increased the responses of column-purified bronchoalveolar lymphocytes.
Our studies demonstrate two mechanisms that limit the responses of canine lung lymphocytes to mitogenic stimulation: a suppression by alveolar macrophages of lymphocyte proliferation and an inherent hyporesponsiveness of bronchoalveolar lymphocytes. These may be of importance in regulating the response of lung to inhaled antigens.