CNRS UMR 5089, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France; Université de Toulouse, Toulouse, France.
Immunol Rev. 2014 Nov;262(1):216-31. doi: 10.1111/imr.12214.
Macrophages are professional migrating cells found in all body tissues from the early embryonic stages till the end of the adult life. Tissue macrophages do not only play beneficial roles. In several diseases, macrophages recruited from blood monocytes have a deleterious action such as favoring cancer progression and destroying tissues in chronic inflammation. To migrate in 3D environments, all leukocytes use the amoeboid movement while macrophages use the amoeboid and the mesenchymal migration modes. Mesenchymal migration takes place in dense matrices and involves podosomes and proteolysis of the extracellular matrix to create paths. Podosome disruption has been correlated with reduced mesenchymal migration of macrophages and unaffected amoeboid migration. Therefore, podosomes are proposed as a therapeutic target. Inhibiting podosome regulators that are only expressed in macrophages and few cell types would avoid collateral effects often encountered when ubiquitous proteins are used as drug targets. With the current status of our knowledge on human macrophage podosomes and 3D migration, the tyrosine kinase Hck appears to be a good candidate.
巨噬细胞是专业的迁移细胞，存在于从胚胎早期到成年期结束的所有身体组织中。组织巨噬细胞不仅发挥有益作用。在几种疾病中，从血液单核细胞募集而来的巨噬细胞具有有害作用，例如促进癌症进展和破坏慢性炎症中的组织。为了在 3D 环境中迁移，所有白细胞都使用变形运动，而巨噬细胞则使用变形运动和间质迁移模式。间质迁移发生在密集的基质中，并涉及足突和细胞外基质的蛋白水解以创建路径。足突破坏与巨噬细胞间质迁移减少和变形运动不受影响有关。因此，足突被提议作为治疗靶点。抑制仅在巨噬细胞和少数细胞类型中表达的足突调节剂可以避免使用普遍存在的蛋白质作为药物靶点时经常遇到的副作用。根据我们目前对人类巨噬细胞足突和 3D 迁移的了解，酪氨酸激酶 Hck 似乎是一个很好的候选者。
