Macrophage migration in fibrin gel matrices.
Macrophage migration in fibrin gel matrices.
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发表时间：
1986
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通讯作者：
P. S. Ciano;R. Colvin;A. Dvorak;J. McDonagh;H. Dvorak
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作者：
P. S. Ciano;R. Colvin;A. Dvorak;J. McDonagh;H. Dvorak
巨噬细胞在体外人工基质上的迁移已经被广泛研究，但在体内，巨噬细胞通过结缔组织和纤维蛋白凝胶网进行迁移，这些组织和纤维蛋白凝胶网构成了许多炎症反应和实体肿瘤的基质。因此，研究人员进行了巨噬细胞在具有或不具有硝化纤维素过滤器支持的更具生物学相关性的基质中的迁移研究。巨噬细胞在纤维蛋白凝胶中的迁移取决于纤维蛋白和凝血酶浓度以及纤维蛋白交联的性质。当纤维蛋白浓度高达5 mg/ml时，与未处理的过滤器相比，仅使用γ链交联时，巨噬细胞迁移增强。然而，当纤维蛋白α链也交联时，巨噬细胞的迁移在大约3 mg/ml纤维蛋白时被抑制，在5 mg/ml纤维蛋白时完全停止。1单位/ml凝血酶浓度有利于巨噬细胞的最大迁移。污染纤维连接蛋白的消耗不影响这些结果。纤维蛋白凝胶的孔径远低于允许巨噬细胞通过硝化纤维素过滤器迁移的最小孔径。因此，为了穿透纤维蛋白凝胶，巨噬细胞可以通过局部纤维蛋白溶解或推开纤维蛋白链来扩大有效孔径。如果纤维蛋白溶解起作用，那么这个过程必须是高度局部的，因为只有少量的纤维蛋白溶解伴随着纤维蛋白凝胶中巨噬细胞的广泛迁移；此外，纤溶抑制剂不影响巨噬细胞的迁移。我们得出结论，在炎症反应和实体肿瘤中沉积的纤维蛋白以促进或抑制巨噬细胞迁移的形式和浓度存在；因此，纤维蛋白可能调节巨噬细胞参与这些和其他病理反应。
Macrophage migration has been extensively studied in vitro on artificial substrates but in vivo macrophages migrate through connective tissue and fibrin gel meshworks that comprise the stroma of many inflammatory reactions and solid tumors. Studies were therefore undertaken to investigate macrophage migration in this more biologically relevant matrix cast either with or without nitrocellulose filter support. Macrophage migration in fibrin gels depended on both fibrin and thrombin concentrations and on the nature of fibrin crosslinking. With gamma-chain crosslinking only, macrophage migration was enhanced as compared with untreated filters at fibrin concentrations of up to 5 mg/ml. However, when fibrin alpha-chains were also crosslinked, as occurs in vivo, macrophage migration was inhibited at approximately 3 mg/ml fibrin and was stopped altogether at 5 mg/ml. Thrombin concentrations of 1 unit/ml favored maximal macrophage migration. Depletion of contaminating fibronectin did not affect these results. The pore size of fibrin gels is well below the minimum that permits macrophage migration through nitrocellulose filters. Thus, to penetrate fibrin gels, macrophages could enlarge effective pore size by local fibrinolysis or by pushing apart fibrin strands. If fibrinolysis is responsible, this process must be highly localized because only small amounts of fibrinolysis accompanied extensive macrophage migration in fibrin gels; moreover, fibrinolysis inhibitors did not affect macrophage migration. We conclude that the fibrin deposited in inflammatory reactions and solid tumors is present in forms and concentrations that either facilitate or inhibit macrophage migration; fibrin may therefore regulate macrophage participation in these and other pathologic reactions.