Dadfar E, Jacobson S H, Lundahl J
Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institutet, Karolinska University Hospital, Sweden.
Clin Exp Immunol. 2007 Jun;148(3):573-82. doi: 10.1111/j.1365-2249.2007.03373.x. Epub 2007 Mar 26.
The transmigration of peripheral human monocytes to the interstitium is a fundamental step in the host-defence mechanism against infections. Little is known about the state of function of in vivo transmigrated interstitial monocytes prior to differentiation into macrophages and dendritic cells. We hypothesized that newly recruited interstitial monocytes have a preserved responsiveness against bacterial-related peptides, giving them a specific role in the immediate defence against invading pathogens. In order to test this hypothesis, we explored the responsiveness of in vivo transmigrated as well as peripheral monocytes, in terms of CD11b expression and H(2)O(2) production towards the bacterial-related peptide formylmethionylleucylphenylalanine (fMLP) by the use of a skin chamber technique. In addition, we analysed the concentration of interleukin (IL)-8, monocyte chemotactic protein-1 (MCP-1) and tumour necrosis factor (TNF)-alpha in the skin blister exudates and in the circulation. We demonstrate that in vivo-transmigrated monocytes had a fivefold higher CD11b expression compared to monocytes obtained from the peripheral circulation. fMLP exposure induced a significantly higher CD11b expression on transmigrated cells compared to peripheral monocytes. In addition, newly recruited monocytes had a preserved H(2)O(2) production. The interstitial concentration of IL-8, MCP-1 and TNF-alpha was significantly higher in blister exudates compared to that in the peripheral circulation. Thus, in vivo transmigrated human monocytes preserve their capacity to respond towards bacterial peptides in terms of CD11b up-regulation and H(2)O(2) generation. These data strengthen a role for newly recruited interstitial human monocytes in the immediate defence against invading pathogens.
外周血人类单核细胞向组织间隙的迁移是宿主抵御感染防御机制中的一个基本步骤。对于体内迁移至组织间隙的单核细胞在分化为巨噬细胞和树突状细胞之前的功能状态,我们知之甚少。我们推测,新招募的组织间隙单核细胞对细菌相关肽具有保留的反应性,使其在抵御入侵病原体的即时防御中发挥特定作用。为了验证这一假设,我们利用皮肤腔室技术,从CD11b表达和H₂O₂产生方面,探究了体内迁移的单核细胞以及外周单核细胞对细菌相关肽甲酰甲硫氨酰亮氨酰苯丙氨酸(fMLP)的反应性。此外,我们分析了皮肤水疱渗出液和循环中白细胞介素(IL)-8、单核细胞趋化蛋白-(MCP-1)和肿瘤坏死因子(TNF)-α的浓度。我们证明,与从外周循环获得的单核细胞相比,体内迁移的单核细胞CD11b表达高五倍。与外周单核细胞相比,fMLP刺激使迁移细胞上的CD11b表达显著更高。此外,新招募的单核细胞保留了H₂O₂产生能力。水疱渗出液中IL-8、MCP-1和TNF-α的组织间隙浓度显著高于外周循环中的浓度。因此,体内迁移的人类单核细胞在CD11b上调和H₂O₂生成方面保留了对细菌肽的反应能力。这些数据支持了新招募的组织间隙人类单核细胞在抵御入侵病原体即时防御中的作用。