Lipopolysaccharide modulates neutrophil recruitment and macrophage polarization on lymphatic vessels and impairs lymphatic function in rat mesentery
Lipopolysaccharide modulates neutrophil recruitment and macrophage polarization on lymphatic vessels and impairs lymphatic function in rat mesentery
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DOI：
10.1152/ajpheart.00467.2015
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发表时间：
2015-12-15
影响因子：
4.8
通讯作者：
Muthuchamy, Mariappan
中科院分区：
文献类型：
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作者：
Chakraborty, Sanjukta;Zawieja, Scott D.;Muthuchamy, Mariappan
淋巴系统的损伤在与内毒素（如LPS）升高有关的多种炎症病理中是明显的。然而，LPS影响淋巴收缩性的直接机制尚不清楚。我们假设，炎症条件下肠系膜内先天免疫细胞群的动态调节扰乱了组织细胞因子/趋化因子的稳态，并随后影响淋巴功能。我们用大鼠腹腔注射LPS （10 mg/kg）来测定肠系膜内先天免疫细胞谱的变化和分离淋巴制剂拉伸介导的收缩反应的变化。结果显示，注射lps的大鼠肠系膜淋巴管的相性收缩活性降低，淋巴泵功能和流量严重受损。LPS组淋巴血管和透明肠系膜上的中性粒细胞数量显著减少，单核/巨噬细胞数量显著增加。这群单核细胞和巨噬细胞建立了强健的M2表型，其中大多数显示CD163和CD206的高表达。注射lps2后，大鼠肠系膜中嗜中性粒细胞和巨噬细胞的几种细胞因子和趋化剂发生了显著变化。LPS处理淋巴肌肉细胞（LMCs）后，黏附分子VCAM1、ICAM1、CXCR2和半乳糖凝集素-9的表达发生显著变化。lps - tlr4介导的lmc中pAKT、pERK pI-kappa B和pMLC20的调节促进了收缩和炎症途径。因此，我们的数据提供了第一个证据，证明在淋巴功能障碍的炎症过程中，淋巴上或淋巴附近的先天免疫细胞和复杂的细胞因子环境的动态变化。
Impairment of the lymphatic system is apparent in multiple inflammatory pathologies connected to elevated endotoxins such as LPS. However, the direct mechanisms by which LPS influences the lymphatic contractility are not well understood. We hypothesized that a dynamic modulation of innate immune cell populations in mesentery under inflammatory conditions perturbs tissue cytokine/chemokine homeostasis and subsequently influences lymphatic function. We used rats that were intraperitoneally injected with LPS (10 mg/kg) to determine the changes in the profiles of innate immune cells in the mesentery and in the stretch-mediated contractile responses of isolated lymphatic preparations. Results demonstrated a reduction in the phasic contractile activity of mesenteric lymphatic vessels from LPS-injected rats and a severe impairment of lymphatic pump function and flow. There was a significant reduction in the number of neutrophils and an increase in monocytes/macrophages present on the lymphatic vessels and in the clear mesentery of the LPS group. This population of monocytes and macrophages established a robust M2 phenotype, with the majority showing high expression of CD163 and CD206. Several cytokines and chemoattractants for neutrophils and macrophages were significantly changed in the mesentery of LPSinjected rats. Treatment of lymphatic muscle cells (LMCs) with LPS showed significant changes in the expression of adhesion molecules, VCAM1, ICAM1, CXCR2, and galectin-9. LPS-TLR4-mediated regulation of pAKT, pERK pI-kappa B, and pMLC20 in LMCs promoted both contractile and inflammatory pathways. Thus, our data provide the first evidence connecting the dynamic changes in innate immune cells on or near the lymphatics and complex cytokine milieu during inflammation with lymphatic dysfunction.