EFFECT OF BRUGIA-MALAYI ON THE GROWTH AND PROLIFERATION OF ENDOTHELIAL-CELLS IN-VITRO

Athymic mice (C3H/HeN) parasitized by Brugia malayi develop massively dilated lymphatics. The lymphatic endothelial lining is perturbed, and numerous mononuclear and giant cells are closely apposed to the endot helium. The hyperplastic endothelial cells and low opening pressure of the lymphatics suggest abnormal multiplication of these cells may be important in the dilation. We studied the in vitro growth rate of huma n umbilical vein endothelial cells cultured with adult worms and micro filariae of B. malayi. The tetrazolium salt reduction assays were used to quantify possible direct mitogenic or inhibitory effects. The grow th factor-induced proliferation of endothelial cells was significantly suppressed by 44-51% on day 1, 46-81% on day 3, and 45-79% on day 5 i n cultures containing adult female worms, which had greater suppressor activity on endothelial cell proliferation than male worms, microfila riae, or soluble adult worm extract. Culture supernatant containing fe male worm excretory-secretory products significantly inhibited the gro wth and multiplication of cells, suggesting that adult female worms re lease antigens or proteins that have inhibitory activity on growth fac tors necessary for endothelial cell proliferation in vitro. Excess hum an recombinant epidermal growth factor and bovine brain extract partly reversed the inhibitory activity of worms in culture and restored the endothelial cell proliferation when incubated with worm culture super natant. Indomethacin and BW 775Hcl failed to restore normal endothelia l proliferation in the presence of female worms, suggesting that paras ite-derived prostanoids and cyclooxygenase products did not cause the inhibition. Lymph from dilated lymphatics, but not serum from infected mice, increased the proliferation of cells in vitro. Together, these data demonstrate that excretory-secretory products of B. malayi parasi tes suppress vascular endothelial proliferation in vitro. Furthermore, increases in the number of these cells in vitro in the presence of ly mph suggest that parasite-induced host factors may be important in mod ulating the degree of proliferation.