Requirement of A1-a for bacillus Calmette-Guerin-mediated protection of macrophages against nitric oxide-induced apoptosis
Requirement of A1-a for bacillus Calmette-Guerin-mediated protection of macrophages against nitric oxide-induced apoptosis
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DOI：
10.4049/jimmunol.166.7.4721
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发表时间：
2001-04-01
影响因子：
4.4
通讯作者：
Prystowsky, MB
中科院分区：
文献类型：
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作者：
Kausalya, S;Somogyi, R;Prystowsky, MB
细胞凋亡在调节细胞内微生物感染过程中的作用尚不清楚。我们研究了小鼠腹腔渗出液巨噬细胞（PEM）和J774巨噬细胞系的凋亡调控与卡介苗（BCG）处理之间的关系。在PEM和J774细胞中，与其它bcl 2家族成员（bcl-w、bcl-2、bcl-xl、bcl-xs、bax、巴克、bad）相比，BCG处理选择性地诱导抗凋亡基因At的mRNA表达。在PEM中，Al表达在感染后8小时达到最大，并被蛋白酶体抑制剂MG-132废除。诱导是独立的蛋白质合成以及p38丝裂原活化蛋白激酶和磷脂酰肌醇3-激酶途径，并不需要活的生物体。三个基因编码密切相关的亚型铝都表达，但铝-a亚型显示最大的倍数诱导PEM。BCG诱导的Al表达与保护宿主巨噬细胞免受PEM和J774细胞中NO介导的凋亡有关。BCG介导的保护作用在源自Al-a（-/-）小鼠的PEM中被废除，表明炎性巨噬细胞的存活需要Al-a。
The role of apoptosis in regulating the course of intracellular microbial infection is not well understood. We studied the relationship between apoptotic regulation and bacillus Calmette-Guierin (BCG) treatment in murine peritoneal exudate macrophages (PEM) and the J774 macrophage cell line. In both PEM and J774 cells, mRNA expression of the anti-apoptotic gene, At, was selectively induced by BCG treatment as compared with other bcl2 family members (bcl-w, bcl-2, bcl-xl, bcl-xs, bax, bak, bad). In PEM, Al expression was maximal by 8 h postinfection and was abrogated by the proteasomal inhibitor MG-132. The induction was independent of protein synthesis as well as the p38 mitogen-activated protein kinase and phospbatidylinositol 3-kinase pathways and did not require live organism. Three genes encoding closely related isoforms of Al were all expressed; however, the Al-a isoform displayed the greatest fold induction in PEM. BCG-induced Al expression was associated with protection of host macrophages from NO-mediated apoptosis in both PEM and J774 cells. BCG-mediated protection was abrogated in PEM derived from Al-a(-/-) mice, indicating a requirement of Al-a for survival of inflammatory macrophages.