Requirement for cell-to-cell contact for the immunosuppressive activity of human alveolar macrophages.
Requirement for cell-to-cell contact for the immunosuppressive activity of human alveolar macrophages.
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人肺泡巨噬细胞的免疫抑制活性需要细胞间接触。
DOI：
10.1165/ajrcmb/4.3.287
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发表时间：
1991
影响因子：
6.4
通讯作者：
Ellner,JJ
中科院分区：
文献类型：
--
作者：
Rich,EA;Cooper,C;Toossi,Z;Leonard,ML;Stucky,RM;Wiblin,RT;Ellner,JJ
研究了健康志愿者支气管肺泡灌洗获得的肺泡巨噬细胞（AM）体外抑制T淋巴细胞对有丝分裂原植物血凝素（PHA）反应的能力。通过掺入[3H]胸腺嘧啶（[3H] TdR）和白细胞介素-2 （IL-2）表达测定，AM而非单核细胞（MN）抑制外周血单核细胞（PBMC）对PHA的反应。然而，不同时期和不同浓度细胞产生的AM上清液并没有抑制PBMC对PHA的反应。为了检验细胞接触对AM抑制活性的作用，将AM或MN直接（共培养）添加到6孔板的PBMC中，或者用0.45'- 1 -'m过滤器分离。两种情况下，MN均未抑制PBMC的成母反应。AM与PBMC比例为1:2时，与PBMC直接培养时，AM对囊胚发育的抑制作用为75 ~ 11%(mean ~ SD, n= 3， P< 0.01)；与靶PBMC物理分离时，AM对囊胚发育无抑制作用。AM与PBMC共培养对pha刺激的IL-2产生的抑制作用达到70%，而AM与PBMC在双腔中分离时对IL-2的产生没有抑制作用。为了评估细胞表面对AM抑制活性的作用，用2%多聚甲醛固定AM和MN。固定和不固定的MN都不能抑制PBMC的成母反应，但固定和不固定的AM抑制反应相似（77%至95%）。AM对PBMC的成母反应的抑制活性不是由于AM的细胞毒性，因为无论在培养中存在AM还是MN， PBMC通常都会排除台盼蓝染料，并释放出相似水平的乳酸脱氢酶活性。这些实验表明，AM对PHA有丝分裂反应的抑制需要细胞表面。由于细胞膜的主要部分是脂质，作为表征抑制活性的第一步，用氯仿/甲醇/水制备的AM有机提取物进行了测试，发现其抑制PBMC对PHA的反应的方式与完整细胞相似。AM提取物的抑制作用是MN提取物的3 ~ 6倍。AM提取物与MN提取物在质量上的不同在于其含有磷脂酰甘油。磷脂酰甘油（toO ~ 400i - g/ml）也能直接抑制PBMC对PHA的反应。AM提取物中还含有疏水蛋白。提取物的抑制活性不受热和胰蛋白酶的影响，但被pronase处理部分减弱。因此，AM抑制淋巴细胞对PHA的反应；抑制活性部分是由于细胞相关的疏水物质可能由脂质和蛋白质组成；并且细胞接触或淋巴细胞与AM之间的密切接触需要介导抑制活性。
The ability of alveolar macrophages (AM) obtained by bronchoalveolar lavage of healthy volunteers to suppress T lymphocyte responses to the mitogen phytohemagglutinin (PHA) in vitro was investigated. AM but not monocytes (MN) inhibited responses of peripheral blood mononuclear cells (PBMC) to PHA as measured by incorporation of [3H] thymidine ([3H] TdR) and interleukin-2 (IL-2) expression. Supernatants of AM generated for various periods and with various concentrations of cells did not, however, inhibit PBMC responses to PHA. To examine the role of cell contact in the inhibitory activity of AM, AM or MN were added to PBMC in 6-well plates either directly (in co-culture) or separated by a 0.45'-l-'m filter. MN did not inhibit PBMC blastogenic responses under either condition. AM at a 1: 2 ratio with PBMC inhibited blastogenesis by 75 ą 11%(mean ą SD, n= 3, P< 0.01) when cultured directly with PBMC but had no inhibitory effect on blastogenesis when physically separated from target PBMC. AM in coculture with PBMC also inhibited PHA-stimulated IL-2 production by 70% but did not inhibit IL-2 production when AM were separated from PBMC in dual chambers. To assess the role of the cell surface in the inhibitory activity of AM, AM and MN were fixed with 2% paraformaldehyde. Neither fixed nor unfixed MN inhibited PBMC blastogenic responses, but both fixed and unfixed AM inhibited responses similarly (77 to 95%). The inhibitory activity of AM on blastogenic responses of PBMC was not due to cytotoxicity of AM since PBMC routinely excluded trypan blue dye and released similar levels of lactate dehydrogenase activity whether AM or MN were present in culture. These experiments suggested that the cell surface was required for suppression by AM of mitogenic responses to PHA. Because a major portion of cell membranes is lipid, as an initial step in characterization of the suppressive activity, organic extracts of AM prepared with chloroform/methanol/water were tested and found to inhibit the PBMC response to PHA in a manner similar to that of the intact cells. Extracts of AM inhibited the response to a 3-to to-fold greater extent than did extracts of MN. The extracts of AM differed qualitatively from the extracts of MN in that they contained phosphatidylglycerol. Phosphatidylglycerol (toO to 400 I-'g/ml) also directly inhibited the PBMC response to PHA. The extracts of AM also contained hydrophobic proteins. The inhibitory activity of the extract was unaffected by heat and trypsin but was partially diminished by treatment with pronase. Thus, AM inhibited lymphocyte responses to PHA; the suppressive activity was, in part, due to a cell-associated hydrophobic material possibly comprised of both lipid and protein; and either cell contact or close proximity between lymphocytes and AM was required for mediation of the suppressive activity.
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犬肺表面活性物质免疫抑制成分的鉴定。
影响因子：
4.4
作者：
M. Ansfield;B. Benson
通讯作者：
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对人肺泡巨噬细胞介导的抗原的淋巴细胞增殖反应。
DOI：
10.5555/uri:pii:002221437790018x
发表时间：
1977
期刊：
The Journal of laboratory and clinical medicine
影响因子：
--
作者：
A. Laughter;R. Martin;J. Twomey
通讯作者：
J. Twomey
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影响因子：
4.4
作者：
J. Stobo
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影响因子：
3.2
作者：
C. Li;L. Yam;K. Lam
通讯作者：
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影响因子：
2.9
作者：
PETERS, WHM;FLEURENJAKOBS, AMM;BONTING, SL
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