Clinical impact of real-time evaluation of the biological activity and degradation of hepatocyte growth factor.
Hepatocyte growth factor (HGF) is essential for injury repair. Despite high HGF levels in chronic ulcers, up-regulation of HGF receptor in ulcer tissue and decreased biological activity of HGF in ulcer secretions have been observed. With a surface plasmon resonance-based method, we assessed the binding of HGF to antibodies, receptors, and the basement membrane and identified binding interactions that are indispensable for the biological activity of HGF. Recombinant HGF (rHGF) lots were tested for activity, structural integrity, and degradation, and the results were verified in an in vitro model of cell injury. Biologically active rHGF, as well as plasma from healthy volunteers, bound to heparan sulphate proteoglycan (HSPG) and to anti-HGF antibodies. Decreased binding to HSPG was the first event in rHGF degradation. This study established the feasibility of identifying patients with chronic inflammation who need exogenous HGF and of using ligand-binding assessment to evaluate rHGF lots for biological activity.
Nayeri
Fariba
F
Division of Infectious Diseases, Faculty of Health Science, University Hospital, Linkoping, Sweden. fariba.nayeri@lio.se
Nayeri
Tayeb
T
Aili
Daniel
D
Brudin
Lars
L
Liedberg
Bo
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001485:Basement Membrane / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D019812:Heparan Sulfate Proteoglycans / Q000737:chemistry; D017228:Hepatocyte Growth Factor / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry; D020349:Surface Plasmon Resonance; D014456:Ulcer / Q000378:metabolism; D014945:Wound Healing
D019812:Heparan Sulfate Proteoglycans; D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor