The effect of integrin antibodies on the attachment and proliferation of human Tenon's capsule fibroblasts.
The integrins are protein heterodimers consisting of noncovalently associated alpha and beta subunits. The adhesive interactions mediated by integrins are necessary for cellular survival and proliferation. In this study we investigated the effects of three different integrin antibodies on the proliferation of human Tenon's capsule fibroblasts in tissue culture. Human Tenon's capsule fibroblasts were cultured into 96 well plates and treated with different concentrations (ranging from 10(-6) to 1 microg ml(-1)) of three different integrin antibodies: human integrin alpha-2 antibody, human integrin alpha-3 antibody and human integrin alpha-5/FnR (fibronectin receptor) antibody. Coulter counter, hexosaminidase, and 3H-thymidine assays were used to determine the inhibitory effects of these integrin antibodies on ocular fibroblasts on days 0 (attachment), 1,3 and 7 following antibody treatment. The concentration of each antibody required to produce a proliferation 50% less than the control (ID50) was calculated for each assay. With respect to attachment, all three antibodies studied displayed some inhibitory activity. All three antibodies also displayed dose-dependent antiproliferative properties, especially at the highest concentration tested after 7 days of exposure. The integrin alpha-2 antibody was the most potent of the inhibitors, followed by the integrin alpha-3 antibody, with the integrin alpha-5 antibody being the least potent antibody tested. In addition, the anti-proliferative activities of the integrin alpha-2 and integrin alpha-3 antibodies increased with increasing incubation time. In conclusion, these integrin antibodies demonstrated some inhibitory effects on the attachment and proliferation of human Tenon's capsule fibroblasts in culture. Further investigation will be required to determine whether integrin antibodies can significantly limit scar formation in vivo without significant toxicity.
Paikal
D
D
Jules Stein Eye Institute, Department of Ophthalmology, UCLA School of Medicine, Los Angeles, CA 90095-7004, USA.
Zhang
G
G
Cheng
Q I
QI
Lee
D A
DA
D000906:Antibodies / Q000737:chemistry / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology; D002452:Cell Count; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D002921:Cicatrix / Q000517:prevention & control; D003124:Colorimetry; D004306:Dose-Response Relationship, Immunologic; D005347:Fibroblasts / Q000276:immunology / Q000473:pathology*; D018463:Filtering Surgery; D005901:Glaucoma / Q000601:surgery; D006801:Humans; D016023:Integrins / Q000276:immunology*; D009994:Osmolar Concentration; D017469:Receptors, Fibronectin / Q000276:immunology*; D012588:Scintillation Counting; D013997:Time Factors; D014129:Trabecular Meshwork / Q000276:immunology / Q000473:pathology*; D016896:Treatment Outcome
D000906:Antibodies; D016023:Integrins; D017469:Receptors, Fibronectin