Biochemical and functional characterization of three activated macrophage populations

Biochemical and functional characterization of three activated macrophage populations
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DOI:
10.1189/jlb.0406249
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发表时间:
2006-12-01
影响因子:
5.5
通讯作者:
Mosser, David M.
Mosser, David M.
中科院分区:
医学3区
文献类型:
--
作者:
Edwards, Justin P.;Zhang, Xia;Mosser, David M.

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我们产生了三个群体的巨噬细胞(M φ)在体外和特征。经典活化的M phi(Ca-3 phi)用IFN-γ致敏并用LPS刺激。II型活化的M phi(M phi-II)类似地引发,但用LPS加免疫复合物刺激。或者,用IL-4引发活化的M phi(AA-M phi)过夜。在这里,我们提出了三种细胞类型的并排比较。我们主要关注M phi-II和AA-M phi之间的差异,因为两者都被归类为M2 M phi,与Ca-M phi不同。我们表明,M φ-II更接近于钙M φ比他们是AA-M φ。M phi-II和Ca-M phi,但不是AA-M phi,产生高水平的NO,并且具有低的脱氢酶活性。AA-M phi表达FIZZ 1,而M phi-II和Ca-M phi都不表达。M phi-II和Ca-M phi表达相对高水平的CD 86,而AA-M phi实际上缺乏这种共刺激分子。Ca-M phi和M phi-II是有效的APC,而AA-M phi不能刺激有效的T细胞增殖。Ca-M phi和M phi-II之间的差异更为微妙。Ca-M phi产生IL-12并产生Th 1细胞,而M phi-II产生高水平的IL-10并因此产生分泌IL-4和IL-10的Th 2细胞。M phi-II表达可用于在组织中鉴定它们的两种标记物。它们是鞘氨醇激酶-1和LIGHT(TNF超家族14)。因此,Ca-M phi、M phi-II和AA-M phi代表具有不同生物学功能的三个细胞群体。
We generated three populations of macrophages (M phi) in vitro and characterized each. Classically activated M phi (Ca-3 phi) were primed with IFN-,y and stimulated with LPS. Type II-activated M phi (M phi-II) were similarly primed but stimulated with LPS plus immune complexes. Alternatively activated M phi (AA-M phi) were primed overnight with IL-4. Here, we present a side-byside comparison of the three cell types. We focus primarily on differences between M phi-II and AA-M phi, as both have been classified as M2 M phi, distinct from Ca-M phi. We show that M phi-II more closely resemble Ca-M phi than they are to AA-M phi. M phi-II and Ca-M phi, but not AA-M phi, produce high levels of NO and have low arginase activity. AA-M phi express FIZZ1, whereas neither M phi-II nor Ca-M phi do. M phi-II and Ca-M phi express relatively high levels of CD86, whereas AA-M phi are virtually devoid of this costimulatory molecule. Ca-M phi and M phi-II are efficient APC, whereas AA-M phi fail to stimulate efficient T cell proliferation. The differences between Ca-M phi and M phi-II are more subtle. Ca-M phi produce IL-12 and give rise to Th1 cells, whereas M phi-II produce high levels of IL-10 and thus, give rise to Th2 cells secreting IL-4 and IL-10. M phi-II express two markers that may be used to identify them in tissue. These are sphingosine kinase-1 and LIGHT (TNF superfamily 14). Thus, Ca-M phi, M phi-II, and AA-M phi represent three populations of cells with different biological functions.