Tumor necrosis factor (TNF) is a potent rat mast cell chemoattractant
Tumor necrosis factor (TNF) is a potent rat mast cell chemoattractant
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DOI：
10.1089/jir.2006.0158
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发表时间：
2007-11-01
影响因子：
2.3
通讯作者：
Misiak-Tloczek, Anna H.
中科院分区：
文献类型：
--
作者：
Brzezinska-Blaszczyk, Ewa;Pietrzak, Anna;Misiak-Tloczek, Anna H.
众所周知，在不同的病理生理条件下，局部组织中的肥大细胞数量会增加，但刺激组织内局部肥大细胞积累的体液因素尚不清楚。考虑到肿瘤坏死因子（TNF）以多种方式影响组织肥大细胞的活性，本研究的目的是研究TNF对大鼠腹膜肥大细胞的趋化活性。我们已经发现，TNF诱导肥大细胞的迁移反应在剂量依赖的方式，即使在缺乏细胞外基质（ECM）蛋白。TNF浓度低至3 fM时，观察到明显的迁移；较高的TNF浓度显著抑制了肥大细胞的自发迁移。在ECM蛋白存在的情况下，TNF以双相方式诱导肥大细胞迁移，迁移峰发生在类似于0.3 fM和60 pM（纤维连接蛋白存在的情况下），以及类似于0.6 fM和600 pM（层粘连蛋白存在的情况下）。在相同的实验条件下，RANTES诱导了剂量依赖性肥大细胞迁移，该趋化因子最大迁移的最佳浓度近似于13 nM。肥大细胞对低浓度TNF的迁移反应是趋化反应，对高浓度TNF的迁移反应是趋化作用。中和抗tnf和抗tnfr1抗体可完全阻断tnf诱导的肥大细胞迁移。酪氨酸激酶抑制剂染料木素显著抑制肥大细胞向TNF的迁移。此外，我们已经证明TNF不会诱导大鼠肥大细胞脱颗粒。综上所述，我们的研究结果表明，TNF作为大鼠肥大细胞的一种非常有效的趋化因子，会导致这些细胞在各种病理生理条件下积聚，并伴有炎症。
It is well known that mast cell number increases in local tissues under different pathophysiologic conditions, although the humoral factors that stimulate local mast cell accumulation within tissues are not yet well known. Taking into account that tumor necrosis factor (TNF) influences tissue mast cell activity in various ways, the aim of the present study was to investigate the chemotactic activity of TNF for rat peritoneal mast cells. We have found that TNF induces mast cell migratory response in a dose-dependent manner, even in the absence of extracellular matrix (ECM) proteins. Significant migration was observed at concentrations of TNF as low as similar to 3 fM; higher TNF concentrations caused significant inhibition of spontaneous mast cell migration. In the presence of ECM proteins, TNF induced migration of mast cells in a biphasic manner, with peaks of migration occurring at similar to 0.3 fM and similar to 60 pM ( in the presence of fibronectin) and at similar to 0.6 fM and similar to 600 pM ( in the presence of laminin). Under the same experimental conditions, RANTES induced dose-dependent mast cell migration, and the optimal concentration of this chemokine for maximal migration was similar to 13 nM. The mast cell migratory response to lower concentrations of TNF was chemotactic and to higher TNF concentrations was due to chemokinesis. TNF-induced mast cell migration was completely blocked by neutralizing anti-TNF and anti-TNFR1 antibodies. The tyrosine kinase inhibitor, genistein, significantly abrogated mast cell migration toward TNF. Additionally, we have documented that TNF does not induce degranulation of rat mast cells. Taken together, our results indicate that TNF serves as an extremely potent chemotactic factor for rat mast cells that would cause accumulation of these cells at the site of diverse pathophysiologic conditions accompanied by inflammation.