G-CSF enhances the adhesion of encephalitogenic T cells to extracellular matrix components: a possible mechanism for exacerbation of multiple sclerosis

J Neuroimmunol. 2006 Mar;172(1-2):145-55. doi: 10.1016/j.jneuroim.2005.11.012. Epub 2006 Jan 4.

Abstract

Autologous stem cell transplantation is being considered as treatment of severe refractory autoimmune disorders, including MS. Stem cell mobilization is achieved with granulocyte-colony stimulating factor (G-CSF), however, G-CSF administration resulted in cases of worsened clinical MS status. We studied autoreactive T-cell properties, which can promote CNS inflammation in MS. We show that G-CSF enhances MS autoreactive T cell line adhesion to the ECM proteins collagen IV and fibronectin as effectively as the proinflammatory IFNgamma and TNFalpha, known to exacerbate MS symptoms. We propose a link between clinical worsening of MS symptoms induced by G-CSF and the hyperstimulation of T cell adhesion to ECM elicited by G-CSF.

Publication types

  • Comparative Study

MeSH terms

  • Blotting, Western / methods
  • Cell Adhesion / drug effects*
  • Cell Count / methods
  • Cytokines / metabolism
  • Cytokines / pharmacology
  • Epistasis, Genetic
  • Extracellular Matrix / metabolism*
  • Focal Adhesion Kinase 2 / metabolism
  • Gene Expression / drug effects
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Hematopoietic Stem Cell Mobilization / methods
  • Humans
  • Integrin alpha1beta1 / metabolism
  • Multiple Sclerosis / pathology*
  • Myelin Basic Protein / pharmacology
  • T-Lymphocytes / drug effects*
  • Time Factors

Substances

  • Cytokines
  • Integrin alpha1beta1
  • Myelin Basic Protein
  • Granulocyte Colony-Stimulating Factor
  • Focal Adhesion Kinase 2