THROMBOSPONDIN AND IN-VIVO ANGIOGENESIS INDUCED BY BASIC FIBROBLAST GROWTH-FACTOR OR LIPOPOLYSACCHARIDE

Purpose. To reexamine the possible effect of human thrombospondin on i n vivo angiogenesis. Methods. In vivo angiogenesis in the rabbit corne a was induced by implants of Elvax-40 sequestering human recombinant b asic fibroblast growth factor (bFGF) or bacterial endotoxin lipopolysa ccharide (LPS). Implants sequestering various concentrations of thromb ospondin were examined for their ability to induce angiogenesis and al so for their possible influence on the angiogenic potential of bFGF- o r LPS-sequestering implants. Results. Constant and reproducible angiog enic stimuli were obtained with implants sequestering 250 ng or more o f bFGF or 100 ng or more of LPS. Implants sequestering 500 ng of throm bospondin induce very little clinical change but larger concentrations induce infiltration of leukocytes and a mild angiogenic stimulus. Com bination of thrombospondin implants with bFGF or LPS implants enhanced the angiogenic response to either of these factors. The thrombospondi n enhancing effect was more prominent when LPS was the stimulating fac tor. Histologic examination of the tested corneas disclosed that the L PS angiogenic stimulus follows the influx of leukocytes. Conversely, t he bFGF angiogenic stimulus appears to be associated with the prolifer ation of stromal keratocytes and corneal epithelial cells. The thrombo spondin angiogenic enhancing effect on both the LPS and bFGF stimuli w as correlated with an increased infiltration of polymorphonuclear cell s. Conclusion. In this system, thrombospondin enhanced the in vivo ang iogenic process induced by bFGF or LPS. This enhancement appears to be associated with an in vivo activation and chemotactic effect on the p olymorphonuclear cells.