Participation of lipopolysaccharide-binding protein in lipopolysaccharide-dependent macrophage activation.

Participation of lipopolysaccharide-binding protein in lipopolysaccharide-dependent macrophage activation.
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DOI:
10.1165/ajrcmb/7.3.239
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发表时间:
1992-09
影响因子:
6.4
通讯作者:
P. Tobias;J. Mathison;Douglas N. Mintz;J. D. Lee;V. Kravchenko;K. Kato;J. Pugin;R. Ulevitch
P. Tobias;J. Mathison;Douglas N. Mintz;J. D. Lee;V. Kravchenko;K. Kato;J. Pugin;R. Ulevitch
中科院分区:
医学1区
文献类型:
--
作者:
P. Tobias;J. Mathison;Douglas N. Mintz;J. D. Lee;V. Kravchenko;K. Kato;J. Pugin;R. Ulevitch

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直到最近才阐明巨噬细胞识别脂多糖(LPS)的机制。与许多配体受体相互作用相反,LPS与其受体CD 14在骨髓细胞上的相互作用通过LPS与LPS结合蛋白(LBP)(一种最近发现的血浆糖蛋白)的预先复合而大大增强。LBP在正常血清或血浆中的含量为5至10微克/毫升。在血浆中,它与LPS快速但短暂地反应。然后LPS-LBP复合物与携带CD 14的细胞反应。用单克隆抗体阻断CD 14或从血浆中去除LBP阻断了细胞与LPS-LBP复合物反应的能力,并且还阻断了细胞因子和其他介质从细胞中的释放。在正常肺中,支气管肺泡灌洗液含有低水平的LBP。然而,在急性肺损伤期间,LBP水平可能通过漏出而升高,并增强肺泡巨噬细胞的活化以释放有害介质。巨噬细胞和其他白细胞识别LPS的这一途径的描述提供了开发新试剂以阻断LPS识别和预防内毒素血症发展的可能性。
Only recently has the mechanism for lipopolysaccharide (LPS) recognition by macrophages been elucidated. In contrast to many ligand receptor interactions, the interaction of LPS with its receptor, CD14, on myeloid cells is greatly enhanced by prior complexation of LPS with LPS-binding protein (LBP), a recently discovered plasma glycoprotein. LBP is found in normal serum or plasma in the 5 to 10 micrograms/ml range. In plasma, it reacts rapidly but transiently with LPS. LPS-LBP complexes then react with CD14 bearing cells. Blocking CD14 with monoclonal antibodies or removal of LBP from plasma blocks the ability of the cells to react with LPS-LBP complexes and also blocks release of cytokines and other mediators from the cells. In the normal lung, bronchoalveolar lavage fluid contains low levels of LBP. However, during acute lung injury, LBP levels may rise by transudation and enhance activation of alveolar macrophages to release injurious mediators. Description of this pathway for LPS recognition by macrophages and other leukocytes offers the possibility of developing new reagents to block LPS recognition and prevent the development of endotoxemia.