Gadolinium chloride alters the acinar distribution of phagocytosis and balance between pro- and anti-inflammatory cytokines
Gadolinium chloride alters the acinar distribution of phagocytosis and balance between pro- and anti-inflammatory cytokines
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DOI：
10.1097/00024382-199610000-00003
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发表时间：
1996-10-01
期刊：
影响因子：
3.1
通讯作者：
Diehl, AM
中科院分区：
文献类型：
--
作者：
Rai, RM;Zhang, JX;Diehl, AM
氯化钆（GdCl 3）通常用于消耗肝脏的枯否细胞（KC），并已显示出降低肝脏吞噬活性和消除某些KC特异性抗原的肝脏表达，然而，GdCl 3处理后KC的确切命运仍不清楚。为了确定GdCl 3是否真的减少了肝脏中KC的总数，我们通过给用生理盐水或GdCl 3处理的大鼠施用荧光标记的乳胶珠来标记具有吞噬活性的KC。通过活体显微镜观察肝脏总荧光和肝腺泡内荧光分布。通过北方印迹分析评估了KCR（一种KC特异性基因产物）和Pu-1（一种普遍存在的单核细胞基因产物）的肝mRNA水平，并比较了促炎因子表达的差异。（肿瘤坏死因子（TNF）-α）和抗炎通过逆转录聚合酶链反应（RT-PCR）评估白细胞介素（IL）-10）细胞因子，我们的研究结果表明，GdCl 3并没有显着减少肝脏中的吞噬活性细胞的数量，但改变了这些细胞的腺泡分布，并可能引起KC表型的开关，使这些细胞不再表达KCR或IL-10。GdCl 3预处理抑制应激相关的IL-10诱导，但未能下调TNF-α的表达。这种表型变化可能具有重要的后果，因为它允许TNF-α的相对过表达。
Gadolinium chloride (GdCl3) is commonly used to deplete the liver of Kupffer cells (KC) and has been shown to decrease hepatic phagocytic activity and to abolish hepatic expression of certain KC-specific antigens, However, the exact fate of the KCs after GdCl3 treatment remains unclear. To determine if GdCl3 actually decreases the total number of KCs in the liver, we labeled phagocytically-active KC by administering fluorescent-labeled latex beads to rats treated with either normal saline or GdCl3. Total hepatic fluorescence and the distribution of fluorescence within liver acini were evaluated by intravital microscopy. Hepatic mRNA levels of KCR, a KC-specific gene product, and Pu-1, a ubiquitous monocyte gene product, were assessed by Northern blot analysis, and differences in the expression of pro-inflammatory (tumor necrosis factor (TNF)-alpha) and anti-inflammatory (interleukin (IL)-10) cytokines were assessed by reverse-transcriptase polymerase chain reaction (RT-PCR), Our results indicate that GdCl3 does not significantly reduce the number of phagocytically active cells in the liver, but alters the acinar distribution of these cells and may provoke a switch in the KC phenotype such that these cells no longer express KCR or IL-10. GdCl3 pretreatment inhibited stress-related induction of IL-10, but failed to down-regulate expression of TNF-alpha. This phenotypic change is likely to have important consequences because it permits relative overexpression of TNF-alpha.