Effect of lipopolysaccharide (LPS) and peptidoglycan (PGN) on human mast cell numbers, cytokine production, and protease composition.
Effect of lipopolysaccharide (LPS) and peptidoglycan (PGN) on human mast cell numbers, cytokine production, and protease composition.
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DOI：
10.1186/1471-2172-9-45
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发表时间：
2008-08-07
期刊：
影响因子：
3
通讯作者：
Metcalfe DD
中科院分区：
文献类型：
--
作者：
Kirshenbaum AS;Swindle E;Kulka M;Wu Y;Metcalfe DD
人肥大细胞（HuMC）成熟发生在与外部环境接触的组织中，将肥大细胞祖细胞和成熟肥大细胞暴露于细菌及其产物。然而，长期或短期暴露于细菌衍生的toll样受体（TLR）配体（如脂多糖（LPS）或肽聚糖（PGN））是否会影响HuMC生物学尚不清楚。在6周的培养中，LPS对HuMC数量的影响最小，但增加了CD 117、类胰蛋白酶和糜蛋白酶的表达。PGN抑制HuMC的发育。对于成熟肥大细胞，LPS在rhSCF（10 ng/ml）存在下增加CD 117、类胰蛋白酶、糜蛋白酶和羧肽酶表达，主要在CD 117低HuMC中。LPS可降低FcεRI的表达和β-氨基己糖苷酶的释放，但对LTC 4和PGD 2的产生无影响。PGN减少HuMC数量;和CD 117和类胰蛋白酶表达。在LPS处理的细胞的短期培养上清液中检测到IL-1β和IL-6（除了IL-8和IL-12之外），并且再现了在LPS存在下观察到的CD 117、类胰蛋白酶、糜蛋白酶和羧肽酶表达的增加。与来自野生型而非TLR 4敲除小鼠的小鼠骨髓源性肥大细胞的比较研究显示小鼠肥大细胞糜酶MMCP-1、MMCP-2和MMCP-4的mRNA增加。PGN抑制HuMC生长，而LPS通过改变细胞因子产生和蛋白酶组成，特别是在低浓度SCF下，对成熟HuMC发挥其主要作用。这些数据证明了细菌产物改变HuMC介质产生、颗粒含量和数量的能力，这可能在HuMC暴露于这些产物的粘膜部位特别相关。
Human mast cell (HuMC) maturation occurs in tissues interfacing with the external environment, exposing both mast cell progenitors and mature mast cells, to bacteria and their products. It is unknown, however, whether long- or short-term exposure to bacteria-derived toll-like receptor (TLR) ligands, such as lipopolysaccharide (LPS) or peptidoglycan (PGN), influences HuMC biology. Over 6 wks of culture, LPS had minimal effect on HuMC numbers but increased CD117, tryptase and chymase expression. PGN inhibited HuMC development. For mature mast cells, LPS in the presence of rhSCF (10 ng/ml) increased CD117, tryptase, chymase and carboxypeptidase expression, primarily in CD117low HuMC. LPS decreased FcεRI expression and β-hexosaminidase release; but had no effect on LTC4 and PGD2 production. PGN reduced HuMC numbers; and CD117 and tryptase expression. IL-1β and IL-6 (in addition to IL-8 and IL-12) were detected in short-term culture supernatants of LPS treated cells, and reproduced the increases in CD117, tryptase, chymase, and carboxypeptidase expression observed in the presence of LPS. Comparative studies with mouse bone marrow-derived mast cells from wild type, but not TLR4 knockout mice, showed increases in mRNA of mouse mast cell chymases MMCP-1, MMCP-2 and MMCP-4. PGN inhibits HuMC growth, while LPS exerts its primary effects on mature HuMC by altering cytokine production and protease composition, particularly at low concentrations of SCF. These data demonstrate the ability of bacterial products to alter HuMC mediator production, granular content, and number which may be particularly relevant at mucosal sites where HuMC are exposed to these products.
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DOI：
10.1084/jem.175.4.1003
发表时间：
1992-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gurish MF;Ghildyal N;McNeil HP;Austen KF;Gillis S;Stevens RL
通讯作者：
Stevens RL
影响因子：
3.1
作者：
BARTON, BE;JACKSON, JV
通讯作者：
JACKSON, JV
影响因子：
2.6
作者：
Kirshenbaum, AS;Akin, C;Metcalfe, DD
通讯作者：
Metcalfe, DD
影响因子：
6.1
作者：
Shimizu, Y;Sakai, K;Schwartz, LB
通讯作者：
Schwartz, LB
影响因子：
56.9
作者：
Pasare, C;Medzhitov, R
通讯作者：
Medzhitov, R