Article
Biomarker selection for M1- and M2-polarized canine microglia/macrophages
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Published: | August 25, 2015 |
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Introduction: Microglia/Macrophages (M/M) are a heterogeneous cell population involved in tissue homeostasis, inflammation and immunity of the central nervous system. Depending on the micromilieu, M/M exhibit different pro- (M1) and anti-inflammatory (M2) phenotypes. Currently, dogs are recognized as a suitable large animal model for human spinal cord injury (SCI). However, the role of alternative M/M polarization in the pathogenesis of naturally occurring canine SCI remains enigmatic so far.
Objectives: Transcriptome analysis of M1- and M2-polarized canine macrophages was performed in order to search for novel polarization-specific biomarkers for canine M/M.
Materials & methods: The transcriptome of in vitro cultured unstimulated (M0), as well as M1- and M2-polarized blood-derived macrophages from six dogs was analyzed employing canine genome 2.0 arrays (Affymetrix). Polarization-specific biomarkers were detected using supervised clustering with a K-nearest-neighbors algorithm and correlation-based feature selection.
Results: Analysis of microarray data identified 6358 probe sets that were differentially expressed in at least one pair-wise comparison (M1 versus M0, M2 versus M0, and M2 versus M1). Gene ontology analysis revealed that M1-polarization was associated with biological processes such as respiratory burst and inflammatory response, whereas M2-polarization was associated with processes such as positive regulation of cell cycle and mitotic spindle organization. Biomarker selection suggested latexin (LXN) and membrane-spanning 4-domains, subfamily A, member 2 (MS4A2) to be the most powerful M1- or M2-polarization specific biomarkers.
Conclusion: The present study allows novel insights into the transcriptome of in vitro polarized canine macrophages and predicts that LXN and MS4A2 are biomarkers for M1- or M2-polarized canine M/M, respectively. Further investigations will concentrate on the expression of these biomarkers in canine SCI.