1Department of Medical Biochemistry, Rm. L01-146.2, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
FASEB J. 2014 Jan;28(1):288-99. doi: 10.1096/fj.13-235911. Epub 2013 Sep 16.
Atherosclerosis is a lipid-driven inflammatory disease of the vessel wall, characterized by the chronic activation of macrophages. We investigated whether the helminth-derived antigens [soluble egg antigens (SEAs)] could modulate macrophage inflammatory responses and protect against atherosclerosis in mice. In bone marrow-derived macrophages, SEAs induce anti-inflammatory macrophages, typified by high levels of IL-10 and reduced secretion of proinflammatory mediators. In hyperlipidemic LDLR(-/-) mice, SEA treatment reduced plaque size by 44%, and plaques were less advanced compared with PBS-injected littermate controls. The atheroprotective effect of SEAs was found to be mainly independent of cholesterol lowering and T-lymphocyte responses but instead could be attributed to diminished myeloid cell activation. SEAs reduced circulating neutrophils and inflammatory Ly6C(high) monocytes, and macrophages showed high IL-10 production. In line with the observed systemic effects, atherosclerotic lesions of SEA-treated mice showed reduced intraplaque inflammation as inflammatory markers [TNF-α, monocyte chemotactic protein 1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and CD68], neutrophil content, and newly recruited macrophages were decreased. We show that SEA treatment protects against atherosclerosis development by dampening inflammatory responses. In the future, helminth-derived components may provide novel opportunities to treat chronic inflammatory diseases, as they diminish systemic inflammation and reduce the activation of immune cells.
动脉粥样硬化是一种血管壁的脂质驱动的炎症性疾病，其特征为巨噬细胞的慢性激活。我们研究了寄生虫来源的抗原（可溶性卵抗原 [SEA]）是否可以调节巨噬细胞炎症反应并预防小鼠的动脉粥样硬化。在骨髓来源的巨噬细胞中，SEA 诱导抗炎型巨噬细胞，其特征为高水平的 IL-10 和促炎介质分泌减少。在高脂血症 LDLR(-/-) 小鼠中，SEA 处理使斑块大小减少了 44%，与 PBS 注射的同窝对照相比，斑块进展较少。SEA 的抗动脉粥样硬化作用主要独立于降胆固醇和 T 淋巴细胞反应，而是归因于骨髓细胞激活的减少。SEA 减少了循环中的中性粒细胞和炎症性 Ly6C(high)单核细胞，并且巨噬细胞表现出高水平的 IL-10 产生。与观察到的全身效应一致，SEA 处理的小鼠的动脉粥样硬化病变显示斑块内炎症减少，炎症标志物 [TNF-α、单核细胞趋化蛋白 1 (MCP-1)、细胞间黏附分子 1 (ICAM-1)、血管细胞黏附分子 1 (VCAM-1) 和 CD68]、中性粒细胞含量和新招募的巨噬细胞减少。我们表明，SEA 处理通过抑制炎症反应来预防动脉粥样硬化的发展。将来，寄生虫来源的成分可能为治疗慢性炎症性疾病提供新的机会，因为它们可以减轻全身炎症并减少免疫细胞的激活。
