Owen C A, Campbell M A, Boukedes S S, Stockley R A, Campbell E J
Department of Medicine, University of Utah Health Sciences Center, Salt Lake City 84132.
Am J Physiol. 1994 Dec;267(6 Pt 1):L775-85. doi: 10.1152/ajplung.1994.267.6.L775.
We have demonstrated that a discrete and naturally occurring subpopulation of human monocytes expresses a neutrophil-like proinflammatory (P) phenotype. P monocytes constitute 20-30% of the circulating monocyte pool and are characterized by 1) avid adherence to extracellular matrix through high-level cell-surface expression of alpha 5-, beta 1-, and beta 2-integrins; 2) high capacity to produce reactive oxygen species; 3) high content of serine proteinases and alpha 1-proteinase inhibitor; and 4) proteolytic activity against a soluble peptide human leukocyte elastase substrate, [3H]elastin, and solid-phase fibronectin, even in the presence of proteinase inhibitors. However, P monocytes express little or no cell-surface HLA-DR antigen, suggesting that they are unable to participate in specific immune responses. In contrast, the remainder of circulating monocytes have a low proinflammatory potential but contain the population of monocytes with high-level expression of HLA-DR antigen. P monocytes can readily be separated from the remainder of monocytes on the basis of 1) their capacity to adhere to fibronectin; and 2) their absent expression of HLA-DR antigen when flow cytometry or immunomagnetic beads are used. Our data indicate that, when recruited to sites of inflammation, P monocytes can either promote resolution of inflammation or contribute to tissue injury.
我们已经证明,人类单核细胞中一个离散且自然存在的亚群表现出类似中性粒细胞的促炎(P)表型。P单核细胞占循环单核细胞池的20%-30%,其特征为:1)通过高水平的α5、β1和β2整合素细胞表面表达而强烈黏附于细胞外基质;2)产生活性氧的能力强;3)丝氨酸蛋白酶和α1-蛋白酶抑制剂含量高;4)即使在存在蛋白酶抑制剂的情况下,对可溶性肽人白细胞弹性蛋白酶底物、[3H]弹性蛋白和固相纤连蛋白也具有蛋白水解活性。然而,P单核细胞很少或不表达细胞表面HLA-DR抗原,这表明它们无法参与特异性免疫反应。相比之下,其余循环单核细胞的促炎潜力较低,但包含HLA-DR抗原高表达的单核细胞群体。基于1)它们黏附于纤连蛋白的能力;2)当使用流式细胞术或免疫磁珠时它们不表达HLA-DR抗原,P单核细胞很容易与其余单核细胞分离。我们的数据表明,当被募集到炎症部位时,P单核细胞既可以促进炎症消退,也可以导致组织损伤。