Effects of ofloxacin on integrin expression on epiphyseal mouse chondrocytes in vitro.
Quinolone-induced arthropathy is an important toxic effect in immature animals that has led to restrictions of the therapeutic use of these antimicrobial agents. The effects of ofloxacin on epiphyseal chondrocytes from 17-day-old mouse foetuses were studied in vitro. Adhesion of the cells to culture dishes was impaired in a concentration-dependent manner and was first perceptible at a concentration of 10 mg ofloxacin/litre medium. A closer analysis by immunomorphological methods showed that the expression of several integrin receptors (beta1, alpha3, alpha5beta1, alphavbeta3) on the chondrocytes was reduced. Again, first alterations occurred at the rather low concentration of 10 mg ofloxacin/litre medium, and at 30 mg ofloxacin/litre medium alpha3- and alpha5beta1 integrins were demonstrable on 50% or less of the cultured cells. Based on these findings in vitro, a new hypothesis for the mechanism of the chondrotoxicity of quinolones is proposed: the ability of these antimicrobials to form chelate complexes with divalent cations could explain why the integrin receptors on chondrocytes are altered after quinolone exposure, since it is well known that the function of the integrin receptor depends on calcium or magnesium ions. Further investigations are under way to study the effects of quinolones on integrin receptors in cartilage in more detail.
Shakibaei
M
M
Institut für Anatomie, Freie Universität Berlin, Königin-Luise Str. 15, D-14195, Berlin, Germany.
Förster
C
C
Merker
H J
HJ
Stahlmann
R
R