Liposomes of phosphatidylcholine and cholesterol induce an M2-like macrophage phenotype reprogrammable to M1 pattern with the involvement of B-1 cells
Liposomes of phosphatidylcholine and cholesterol induce an M2-like macrophage phenotype reprogrammable to M1 pattern with the involvement of B-1 cells
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DOI：
10.1016/j.imbio.2014.01.006
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发表时间：
2014-06-01
期刊：
影响因子：
2.8
通讯作者：
Eliana Lanio, Maria
中科院分区：
文献类型：
--
作者：
Cruz-Leal, Yoelys;Lucatelli Laurindo, Maria Fernanda;Eliana Lanio, Maria
巨噬细胞对内源性和非自身刺激的反应分别对应于经典或替代激活的M1或M2表型。B-1细胞通过分泌白细胞介素（IL）-10在调节巨噬细胞极化中的作用已得到证实。然而，B-1细胞对抑制其分泌IL-10能力的免疫原诱导的巨噬细胞表型的影响尚未被探索。本文研究了二棕榈酰磷脂酰胆碱（DPPC）和胆固醇（Chol）脂质体（LipDPPC/OVA）诱导的腹腔巨噬细胞极化模式以及B-1细胞参与巨噬细胞极化的情况。用LPS DPPC/OVA和可溶性OVA（PBS/OVA）免疫BALB B/c、B-1细胞缺陷型BALB B/xid和C57 BL/6小鼠，分析其腹膜细胞，并在体外用脂多糖（LPS）刺激或不刺激。用Lp DPPC/OVA免疫的BALB/c和C57 BL/6小鼠的腹腔巨噬细胞显示M2样表型，这通过它们在没有LPS刺激的情况下的高的β-淀粉酶活性来证明。在刺激后，这些巨噬细胞可重新编程为M1表型，一氧化氮（NO）上调和IL-10分泌减少。此外，在用Lp DPPC/OVA免疫的BALB/c和C57 BL/6小鼠的腹膜细胞的培养上清液中检测到高IFN-γ水平。然而，仍然发现高水平的腺苷酸酶活性和不可检测的IL-12水平，表明向经典活化状态的转换是不完全的。在来自脂质体免疫的BALB/xid小鼠的腹膜细胞中，脱氢酶活性、NO和IL-6的水平低于来自野生型动物的水平，但后两种产物在B-1细胞过继转移后恢复，同时IFN-γ分泌增加。综上所述，我们已经证明，Lp DPPC/OVA诱导腹腔巨噬细胞在LPS刺激后可重编程为M1表型的M2样模式，其中涉及B-1细胞。(C)2014 Elsevier GmbH. All rights reserved.
Macrophages respond to endogenous and non-self stimuli acquiring the M1 or M2 phenotypes, corresponding to classical or alternative activation, respectively. The role of B-1 cells in the regulation of macrophage polarization through the secretion of interleukin (IL)-10 has been demonstrated. However, the influence of B-1 cells on macrophage phenotype induction by an immunogen that suppress their ability to secrete IL-10 has not been explored. Here, we studied the peritoneal macrophage pattern induced by liposomes comprised of dipalmitoylphosphatidylcholine (DPPC) and cholesterol (Chol) carrying ovalbumin (OVA) (Lp DPPC/OVA), and the involvement of B-1 cells in macrophage polarization. Peritoneal cells from BALB/c, B-1 cells-deficient BALB/xid and C57BL/6 mice immunized with Lp DPPC/OVA and OVA in soluble form (PBS/OVA) were analyzed and stimulated or not in vitro with lipopolysaccharide (LPS). Peritoneal macrophages from BALB/c and C57BL/6 mice immunized with Lp DPPC/OVA showed an M2-like phenotype as evidenced by their high arginase activity without LPS stimulation. Upon stimulation, these macrophages were reprogrammable toward the M1 phenotype with the upregulation of nitric oxide (NO) and a decrease in IL-10 secretion. In addition, high IFN-gamma levels were detected in the culture supernatant of peritoneal cells from BALB/c and C57BL/6 mice immunized with Lp DPPC/OVA. Nevertheless, still high levels of arginase activity and undetectable levels of IL-12 were found, indicating that the switch to a classical activation state was not complete. In the peritoneal cells from liposomes-immunized BALB/xid mice, levels of arginase activity, NO, and IL-6 were below those from wild type animals, but the last two products were restored upon adoptive transfer of B-1 cells, together with an increase in IFN-gamma secretion. Summarizing, we have demonstrated that Lp DPPC/OVA induce an M2-like pattern in peritoneal macrophages reprogrammable to M1 phenotype after LPS stimulation, with the involvement of B-1 cells. (C) 2014 Elsevier GmbH. All rights reserved.