Purpose: To reexamine the possible effect of human thrombospondin on in vivo angiogenesis.
Methods: In vivo angiogenesis in the rabbit cornea was induced by implants of Elvax-40 sequestering human recombinant basic fibroblast growth factor (bFGF) or bacterial endotoxin lipopolysaccharide (LPS). Implants sequestering various concentrations of thrombospondin were examined for their ability to induce angiogenesis and also for their possible influence on the angiogenic potential of bFGF- or LPS-sequestering implants.
Results: Constant and reproducible angiogenic stimuli were obtained with implants sequestering 250 ng or more of bFGF or 100 ng or more of LPS. Implants sequestering 500 ng of thrombospondin induce very little clinical change but larger concentrations induce infiltration of leukocytes and a mild angiogenic stimulus. Combination of thrombospondin implants with bFGF or LPS implants enhanced the angiogenic response to either of these factors. The thrombospondin enhancing effect was more prominent when LPS was the stimulating factor. Histologic examination of the tested corneas disclosed that the LPS angiogenic stimulus follows the influx of leukocytes. Conversely, the bFGF angiogenic stimulus appears to be associated with the proliferation of stromal keratocytes and corneal epithelial cells. The thrombospondin angiogenic enhancing effect on both the LPS and bFGF stimuli was correlated with an increased infiltration of polymorphonuclear cells.
Conclusion: In this system, thrombospondin enhanced the in vivo angiogenic process induced by bFGF or LPS. This enhancement appears to be associated with an in vivo activation and chemotactic effect on the polymorphonuclear cells.