REGULATION OF INVITRO CAPILLARY-TUBE FORMATION BY ANTI-INTEGRIN ANTIBODIES

Human endothelial cells are induced to form an anastomosing network of capillary tubes on a gel of collagen I in the presence of PMA. We sho w here that the addition of mAbs, AK7, or RMAC11 directed to the alpha chain of the major collagen receptor on endothelial cells, the integr in alpha2beta1, enhance the number, length, and width of capillary tub es formed by endothelial cells derived from umbilical vein or neonatal foreskins. The anti-alpha2beta1 antibodies maintained the endothelial cells in a rounded morphology and inhibited both their attachment to and proliferation on collagen but not on fibronectin, laminin, or gela tin matrices. Furthermore, RMAC11 promoted tube formation in collagen gels of increased density which in the absence of RMAC11 did not allow tube formation. Neither RMAC11 or AK7 enhanced capillary formation in the absence of PMA. Lumen structure and size were also altered by ant ibody RMAC11. In the absence of antibody the majority of lumina were f ormed intracellularly from single cells, but in die presence of RMAC11 , multiple cells were involved and the lumen size was correspondingly increased. Endothelial cells were also induced to undergo capillary fo rmation in fibrin gels after PMA stimulation. The addition of anti-alp ha(v)beta3 antibodies promoted tube formation in fibrin gels and inhib ited EC adhesion to and proliferation on a fibrinogen matrix. The enha ncement of capillary formation by the anti-integrin antibodies was mat rix specific; that is, anti-alpha(v)beta3 antibodies only enhanced tub e formation on fibrin gels and not on collagen gels while anti-alpha(v )beta1 antibodies only enhanced tubes on collagen and not on fibrin ge ls. Thus we postulate that changes in the adhesive nature of endotheli al cells for their extracellular matrix can profoundly effect their fu nction. Anti-integrin antibodies which inhibit cell-matrix interaction s convert endothelial cells from a proliferative phenotype towards dif ferentiation which results in enhanced capillary tube formation.