Hasday J D, Dubin W, Mongovin S, Goldblum S E, Swoveland P, Leturcq D J, Moriarty A M, Bleecker E R, Martin T R
Department of Medicine, University of Maryland Medical School, Baltimore, USA.
Am J Physiol. 1997 May;272(5 Pt 1):L925-33. doi: 10.1152/ajplung.1997.272.5.L925.
The bacterial endotoxin [lipopolysaccharide (LPS)]-binding protein CD14 modulates the host response to LPS, but membrane-associated and soluble forms of the molecule exert different biological effects. CD14 anchored to the mononuclear phagocyte membrane (mCD14) enhances response to LPS. Soluble CD14 (sCD14) may block LPS stimulation of CD14-bearing cells while supporting LPS presentation to non-CD14-bearing cells. We analyzed cell mCD14 and sCD14 expression in simultaneously collected human bronchoalveolar macrophages (BAM) and peripheral blood monocytes (PBM). Expression of mCD14 in freshly isolated BAM was only 9% as high as in PBM. Levels of sCD14 in 48 h in BAM culture supernatants were 19% as high as in PBM cultures. Interleukin (IL)-6 increased CD14 expression in both BAM and PBM but exerted different effects on CD14 distribution in these cell types. IL-6 increased only sCD14 release (2.5-fold) in BAM while increasing only mCD14 expression (2.5-fold) in PBM. IL-4 reduced both mCD14 (> 40%) and sCD14 (> 60%) expression in both cell types. We speculate that the balance between sCD14 and mCD14 expression influences the response to aspirated or inhaled LPS in the bronchoalveolar compartment. Cytokine expression and monocyte recruitment may influence this process by modulating CD14 expression.
细菌内毒素[脂多糖(LPS)]结合蛋白CD14可调节宿主对LPS的反应,但该分子的膜相关形式和可溶性形式发挥不同的生物学效应。锚定在单核吞噬细胞膜上的CD14(mCD14)可增强对LPS的反应。可溶性CD14(sCD14)可能会阻断LPS对携带CD14细胞的刺激,同时支持将LPS呈递给不携带CD14的细胞。我们分析了同时采集的人支气管肺泡巨噬细胞(BAM)和外周血单核细胞(PBM)中细胞mCD14和sCD14的表达。新鲜分离的BAM中mCD14的表达仅为PBM中的9%。BAM培养上清液中48小时的sCD14水平仅为PBM培养物中的19%。白细胞介素(IL)-6可增加BAM和PBM中CD14的表达,但对这些细胞类型中CD14分布的影响不同。IL-6仅增加BAM中sCD14的释放(2.5倍),而仅增加PBM中mCD14的表达(2.5倍)。IL-4可降低两种细胞类型中mCD14(>40%)和sCD14(>60%)的表达。我们推测,sCD14和mCD14表达之间的平衡会影响支气管肺泡腔对吸入或吸入LPS的反应。细胞因子表达和单核细胞募集可能通过调节CD14表达来影响这一过程。