LIPOPOLYSACCHARIDE BINDING-PROTEIN ENHANCES THE RESPONSIVENESS OF ALVEOLAR MACROPHAGES TO BACTERIAL LIPOPOLYSACCHARIDE - IMPLICATIONS FOR CYTOKINE PRODUCTION IN NORMAL AND INJURED LUNGS
LIPOPOLYSACCHARIDE BINDING-PROTEIN ENHANCES THE RESPONSIVENESS OF ALVEOLAR MACROPHAGES TO BACTERIAL LIPOPOLYSACCHARIDE - IMPLICATIONS FOR CYTOKINE PRODUCTION IN NORMAL AND INJURED LUNGS
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DOI：
10.1172/jci116106
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发表时间：
1992-12-01
影响因子：
15.9
通讯作者：
ULEVITCH, RJ
中科院分区：
文献类型：
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作者：
MARTIN, TR;MATHISON, JC;ULEVITCH, RJ
血浆脂多糖（LPS）结合蛋白（LBP）已被证明可调节兔腹腔巨噬细胞和人血单核细胞对内毒素（LPS）的反应。我们研究了LBP是否存在于肺液中以及LBP对肺巨噬细胞对LPS的反应的影响。通过免疫沉淀法、蛋白质印迹法以及特异性免疫测定法，可以在成人呼吸窘迫综合征患者的灌洗液中检测到免疫反应性LBP。在兔中，LBP似乎起源于肺外，因为LBP的mRNA转录物在来自肝脏的总细胞RNA中被鉴定，但不是来自肺匀浆或肺泡巨噬细胞。纯化的LBP增强人和兔肺泡巨噬细胞对光滑形式LPS（大肠杆菌0111 B：4）和粗糙形式LPS（沙门氏菌Re 595）的反应。在存在LBP和LPS的情况下，肿瘤坏死因子-α（TNFalpha）的产生发生得更早，并且在两种类型的LPS的LPS阈值剂量低1，000倍的情况下。在兔肺泡巨噬细胞与LBP和LPS处理，TNF α mRNA出现更早，达到更高的水平，并有延长的半衰期相比，单独的LPS处理。LPS、LPS和LBP均不影响肺泡巨噬细胞的pH（i）和[Ca（i）++]。CD 14是一种结合LPS/LBP复合物的受体，其特异性单克隆抗体可抑制LPS单独刺激或LPS/LBP复合物刺激的人肺泡巨噬细胞产生TNF α，表明CD 14在介导LPS对肺泡巨噬细胞作用中的重要性。因此，免疫反应性LBP在肺损伤患者的肺灌洗液中积累，并通过依赖于CD 14受体的途径增强肺泡巨噬细胞中LPS刺激的TNF α基因表达。LBP可能在肺内肺泡巨噬细胞增加TNF α表达中起重要作用。
A plasma lipopolysaccharide (LPS)-binding protein (LBP) has been shown to regulate the response of rabbit peritoneal macrophages and human blood monocytes to endotoxin (LPS). We investigated whether LBP is present in lung fluids and the effects of LBP on the response of lung macrophages to LPS. Immunoreactive LBP was detectable in the lavage fluids of patients with the adult respiratory distress syndrome by immunoprecipitation followed by Western blotting, and also by specific immunoassay. In rabbits, the LBP appeared to originate outside of the lungs, inasmuch as mRNA transcripts for LBP were identified in total cellular RNA from liver, but not from lung homogenates or alveolar macrophages. Purified LBP enhanced the response of human and rabbit alveolar macrophages to both smooth form LPS (Escherichia coli 0111 B:4) and rough form LPS (Salmonella minnesota Re595). In the presence of LBP and LPS, the onset of tumor necrosis factor-alpha (TNFalpha) production occurred earlier and at an LPS threshold dose that was as much as 1,000-fold lower for both types of LPS. In rabbit alveolar macrophages treated with LBP and LPS, TNFalpha mRNA appeared earlier, reached higher levels, and had a prolonged half-life as compared with LPS treatment alone. Neither LPS nor LPS and LBP affected pH(i) or [Ca(i)++] in alveolar macrophages. Specific monoclonal antibodies to CD14, a receptor that binds LPS/LBP complexes, inhibited TNFalpha production by human alveolar macrophages stimulated with LPS alone or with LPS/LBP complexes, indicating the importance of CD14 in mediating the effects of LPS on alveolar macrophages. Thus, immunoreactive LBP accumulates in lung lavage fluids in patients with lung injury and enhances LPS-stimulated TNFalpha gene expression in alveolar macrophages by a pathway that depends on the CD14 receptor. LBP may play an important role in augmenting TNFalpha expression by alveolar macrophages within the lungs.