Neutrophil CD14: biochemical properties and role in the secretion of tumor necrosis factor-alpha in response to lipopolysaccharide.

Neutrophil CD14: biochemical properties and role in the secretion of tumor necrosis factor-alpha in response to lipopolysaccharide.
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DOI:
10.4049/jimmunol.150.12.5556
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发表时间:
1993-06
影响因子:
4.4
通讯作者:
A. Haziot;B. Tsuberi;S. Goyert
A. Haziot;B. Tsuberi;S. Goyert
中科院分区:
医学2区
文献类型:
--
作者:
A. Haziot;B. Tsuberi;S. Goyert

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CD 14是主要由单核细胞和巨噬细胞表达的髓样细胞分化抗原。最近已经显示CD 14作为LPS和LPS结合蛋白(LBP)的复合物的受体起作用,LPS结合蛋白是也以痕量存在于正常血清中的急性期血清蛋白。在LBP的存在下,LPS通过CD 14强烈激活单核细胞,如通过TNF分泌所测量的。这种单核细胞活化途径被认为是内毒素休克症状的主要原因。参与革兰氏阴性感染应答的另一种主要细胞类型是嗜中性粒细胞。最近的研究表明,中性粒细胞也表达CD 14,并表明它们可以通过类似的途径对LPS作出反应。然而,嗜中性粒细胞CD 14的生物化学性质以前没有被描述过。在本报告中,我们分析了中性粒细胞CD 14的几个生化特征。我们发现,CD 14是积极合成的中性粒细胞作为糖基磷脂酰肌醇锚定蛋白,从单核细胞CD 14的大小难以区分。此外,嗜中性粒细胞,如单核细胞,脱落到培养上清液中的可溶性形式的CD 14的较小。此外,与单核细胞一样,嗜中性粒细胞通过释放TNF-α经由CD 14对LPS/LBP复合物作出响应。中性粒细胞CD 14的性质和功能表明,它可能直接参与急性炎症反应和内毒素休克。
CD14 is a myeloid cell differentiation Ag expressed primarily by monocytes and macrophages. CD14 has recently been shown to function as a receptor for a complex of LPS and LPS binding protein (LBP), an acute phase serum protein also present in normal serum in trace amounts. In the presence of LBP, LPS strongly activates monocytes via CD14 as measured by TNF secretion. This pathway of monocyte activation is thought to be a major contributor to the symptoms of endotoxin shock. Another major cell type involved in the response to Gram-negative infection is the neutrophil. Recent studies have shown that neutrophils also express CD14 and suggest that they can respond to LPS through a similar pathway. However, the biochemical nature of neutrophil CD14 has not previously been described. In this report, we have analyzed several biochemical characteristics of neutrophil CD14. We show that CD14 is actively synthesized by neutrophils as a glycosylphosphatidyl-inositol-anchored protein, indistinguishable in size from monocyte CD14. Furthermore, neutrophils, like monocytes, shed a smaller soluble form of CD14 into culture supernatants. In addition, like monocytes, neutrophils respond to LPS/LBP complexes via CD14 by releasing TNF-alpha. The described properties and function of neutrophil CD14 suggest that it may directly participate in the acute inflammatory response and in endotoxin shock.