G-CSF enhances the adhesion of encephalitogenic T cells to extracellular matrix components: a possible mechanism for exacerbation of multiple sclerosis.
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.
Snir
Omri
O
Faculty of Life Science, Bar-Ilan University, Ramat-Gan, Israel.
Lavie
Gad
G
Achiron
Anat
A
Bank
Ilan
I
Ben-Aharon
Taya
T
Sredni
Benjamin
B
Cohen
Irun R
IR
Mandel
Mathilda
M
D015153:Blotting, Western / Q000379:methods; D002448:Cell Adhesion / Q000187:drug effects*; D002452:Cell Count / Q000379:methods; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D004843:Epistasis, Genetic; D005109:Extracellular Matrix / Q000378:metabolism*; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D006801:Humans; D039222:Integrin alpha1beta1 / Q000378:metabolism; D009103:Multiple Sclerosis / Q000473:pathology*; D004676:Myelin Basic Protein / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects*; D013997:Time Factors
D016207:Cytokines; D039222:Integrin alpha1beta1; D004676:Myelin Basic Protein; D016179:Granulocyte Colony-Stimulating Factor; D051418:Focal Adhesion Kinase 2