Host Defense Peptide LL-37 Selectively Reduces Proinflammatory Macrophage Responses
Host Defense Peptide LL-37 Selectively Reduces Proinflammatory Macrophage Responses
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DOI：
10.4049/jimmunol.1002508
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发表时间：
2011-05-01
影响因子：
4.4
通讯作者：
Johnson, Pauline
中科院分区：
文献类型：
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作者：
Brown, Kelly L.;Poon, Grace F. T.;Johnson, Pauline
人凯萨林菌素肽LL-37是一种宿主防御肽，具有广泛的免疫调节活性和适度的直接抗微生物性质。LL-37可发挥促炎和抗炎作用，并可调节人外周血单核细胞和上皮细胞的促炎反应。在这项研究中，我们评估了LL-37对小鼠骨髓源性巨噬细胞（BMDM）和组织巨噬细胞在体外和体内的作用。LL-37显著降低LPS和IFN-γ极化的M1-BMDM产生的TNF-α和NO水平，并轻微降低这些细胞产生的活性氧。LL-37不影响IL-4极化的M2-BMDM上调TNF-α酶活性的能力，尽管它确实抑制了这些细胞中LPS诱导的TNF-α分泌。LL-37不损害M1极化BMDM吞噬和杀死细菌的能力，也不影响M2极化BMDM对凋亡中性粒细胞的摄取。然而，LL-37处理的M1-BMDM在体外抑制肿瘤生长方面更有效。LL-37显著降低离体肺泡巨噬细胞中LPS诱导的TNF-α分泌，而其对腹膜巨噬细胞的作用则不那么显著。当通过气管内注射施用LL-37时，在体内也发生LPS诱导的肺泡巨噬细胞的TNF-α分泌的有效抑制。这表明LL-37的选择性能力，以减少M1-BMDM，M2-BMDM，和组织巨噬细胞产生的促炎细胞因子TNF-α响应LPS，而留下其他关键的抗炎M1和M2巨噬细胞功能不变。免疫学杂志，2011，186：5497-5505。
The human cathelicidin peptide, LL-37, is a host defense peptide with a wide range of immunomodulatory activities and modest direct antimicrobial properties. LL-37 can exert both pro- and anti-inflammatory effects and can modulate the proinflammatory responses of human peripheral blood monocytes and epithelial cells. In this study, we evaluated the effect of LL-37 on mouse bone marrow-derived macrophages (BMDM) and tissue macrophages in vitro and in vivo. LL-37 dramatically reduced TNF-alpha and NO levels produced by LPS and IFN-gamma-polarized M1-BMDM and slightly reduced reactive oxygen species production by these cells. LL-37 did not affect the ability of IL-4-polarized M2-BMDM to upregulate arginase activity, although it did inhibit LPS-induced TNF-alpha secretion in these cells. LL-37 did not compromise the ability of M1-polarized BMDM to phagocytose and kill bacteria and did not affect the uptake of apoptotic neutrophils by M2-polarized BMDM. However, LL-37-treated M1-BMDM were more efficient at suppressing tumor growth in vitro. LL-37 significantly reduced LPS-induced TNF-alpha secretion in ex vivo alveolar macrophages, whereas its effect on peritoneal macrophages was much less dramatic. Effective inhibition of LPS-induced TNF-alpha secretion by alveolar macrophages also occurred in vivo when LL-37 was administered by intratracheal injection. This demonstrates a selective ability of LL-37 to decrease M1-BMDM, M2-BMDM, and tissue macrophage production of the proinflammatory cytokine TNF-alpha in response to LPS while leaving other crucial anti-inflammatory M1 and M2 macrophage functions unaltered. The Journal of Immunology, 2011, 186: 5497-5505.