Macrophage function in response to PGE2, L-arginine deprivation, and activation by colony-stimulating factors is dependent on hematopoietic stimulus.
Macrophage function in response to PGE2, L-arginine deprivation, and activation by colony-stimulating factors is dependent on hematopoietic stimulus.
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巨噬细胞对 PGE2、L-精氨酸剥夺和集落刺激因子激活的反应依赖于造血刺激。
DOI：
10.1002/jlb.52.2.228
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发表时间：
1992
影响因子：
5.5
通讯作者：
Schook,LB
中科院分区：
文献类型：
--
作者：
Rutherford,MS;Schook,LB
比较不同巨噬细胞制剂在高前列腺素E2（PGE2）或低l-精氨酸浓度条件下的功能能力。使用集落刺激因子1 （CSF-1）作为骨髓生成刺激的体外骨髓祖细胞（骨髓源性巨噬细胞，bmdm）衍生的巨噬细胞比使用粒细胞-巨噬细胞集落刺激因子（GM-GSF）衍生的巨噬细胞对pge2诱导的肿瘤坏死因子a （TNF-α）分泌的抑制更敏感。pge2没有抑制BMDM群体对L929细胞（TNF-α敏感）的直接细胞溶解，只有gm - csf来源的巨噬细胞对TNF-α -耐药的K562靶点的杀伤能力下降。外源性cAMP抑制两种BMDM群体的TNF-α分泌，但不抑制亚硝酸盐分泌。与csf -1来源的巨噬细胞相比，gm - gsf来源的巨噬细胞在pge2治疗后积累的cAMP更少。从培养基中去除l-精氨酸不会抑制细胞毒性或pge2的分泌，但去除l-精氨酸会阻断干扰素-γ +脂多糖（LPS）激活的gm - csf来源的巨噬细胞特异性的李斯特菌活性。单独使用CSF-1或GM-CSF治疗并不能激活巨噬细胞，但GM-CSF有效地启动了两个BMDM群体，以增强TNF-α分泌，以响应LPS的二次刺激。然而，GM-CSF仅通过csf -1来源的巨噬细胞增强了lps诱导的亚硝酸盐和pge2的产生。这些结果表明，基于造血刺激（巨噬细胞来源于造血刺激）和病变中存在的特定条件，炎症部位内巨噬细胞可能存在差异功能。
Different macrophage preparations were compared for functional capacity in conditions of high prostaglandin E2(PGE2) or low l-arginine concentrations. Macrophages derived in vitro from bone marrow progenitor cells (bone marrow-derived macrophages, BMDMs) using colony-stimulating factor 1 (CSF-1) as the myelopoietic stimulus displayed a greater sensitivity to PGE2-induced suppression of tumor necrosis factor a (TNF-α) secretion than did macrophages derived using granulocyte-macrophage colony-stimulating factor (GM-GSF). Neither BMDM population was inhibited by PGE2for the direct cytolysis of L929 cells (TNF-α sensitive), and only GM-CSF–derived macrophages showed decreased killing of TNF-α–resistant K562 targets. Exogenous cAMP inhibited TNF-α secretion, but not nitrite secretion, by both BMDM populations. GM-GSF–derived macrophages accumulated less cAMP following PGE2treatment than did CSF-1–derived macrophages. Removing l-arginine from the medium did not inhibit cytotoxicity or PGE2secretion, but the listeriacidal activity specific to interferon-γ plus lipopolysaccharide (LPS)-activated GM-CSF–derived macrophages was blocked by removal of l-arginine. Treatment with CSF-1 or GM-CSF alone did not activate the macrophages, but GM-CSF efficiently primed both BMDM populations for augmented TNF-α secretion in response to secondary stimulation using LPS. However, GM-CSF augmented the LPS-induced production of nitrite and PGE2by CSF-1–derived macrophages only. These results demonstrate the potential for differential macrophage function within inflammatory sites based on the hematopoietic stimulus under which the macrophage is derived and the specific conditions present in the lesion.