Classically and alternatively activated bone marrow derived macrophages differ in cytoskeletal functions and migration towards specific CNS cell types

Journal of Neuroinflammation

Charlotte E Teunissen³  Christine D Dijkstra²  Elga HE de Vries²  Wia Baron¹  Priscilla DAM Heijnen²  Elly JF Vereyken² 

[1] University Medical Center Groningen University of Groningen, Dept. Cell Biology, Section Membrane Cell Biology, Groningen, the Netherlands;Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, the Netherlands;Department of Clinical chemistry, VU University Medical Center, Amsterdam, the Netherlands

关键词: neurons;    central nervous system;    alternatively activated macrophages;    classically activated macrophages;    migration;   

Others  :  1213333
DOI  :  10.1186/1742-2094-8-58

 received in 2011-02-17, accepted in 2011-05-26,  发布年份 2011

【 摘 要 】

Background

Macrophages play an important role in neuroinflammatory diseases such as multiple sclerosis (MS) and spinal cord injury (SCI), being involved in both damage and repair. The divergent effects of macrophages might be explained by their different activation status: classically activated (CA/M1), pro-inflammatory, macrophages and alternatively activated (AA/M2), growth promoting, macrophages. Little is known about the effect of macrophages with these phenotypes in the central nervous system (CNS) and how they influence pathogenesis. The aim of this study was therefore to determine the characteristics of these phenotypically different macrophages in the context of the CNS in an in vitro setting.

Results

Here we show that bone marrow derived CA and AA macrophages have a distinct migratory capacity towards medium conditioned by various cell types of the CNS. AA macrophages were preferentially attracted by the low weight (< 10 kD) fraction of neuronal conditioned medium, while CA macrophages were attracted in higher numbers by astrocyte- and oligodendrocyte conditioned medium. Intrinsic motility was twice as high in AA macrophages compared to CA macrophages. The adhesion to extracellular matrix molecules (ECM) was significantly enhanced in CA macrophages compared to control and AA macrophages. The actin cytoskeleton was differentially organized between CA and AA macrophages, possibly due to greater activity of the GTPases RhoA and Rac in CA macrophages. Phagocytosis of myelin and neuronal fragments was increased in CA macrophages compared to AA macrophages. The increase in myelin phagocytosis was associated with higher expression of CR3/MAC-1 in CA macrophages.

Conclusion

In conclusion, since AA macrophages are more motile and are attracted by NCM, they are prone to migrate towards neurons in the CNS. CA macrophages have a lower motility and a stronger adhesion to ECM. In neuroinflammatory diseases the restricted migration and motility of CA macrophages might limit lesion size due to bystander damage.

【 授权许可】

   
2011 Vereyken et al; licensee BioMed Central Ltd.

【 图 表 】

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