GLUCOSAMINYLMURAMYL DIPEPTIDE (GMDP) MODULATES ENDOTHELIAL-CELL ACTIVITIES IN-VITRO BUT HAS NO EFFECT ON ANGIOGENESIS IN-VIVO

Objective and Design: The aim of the study was to evaluate the effects of GMDP on angiogenesis in vivo and as a modulator of human umbilical vein endothelial cell proliferation, cell surface antigen expression and cell adhesion in vitro. Materials: Human umbilical vein endothelia l cells (HUVEC), fertilized white leghorn chicken eggs, antibodies aga inst adhesion molecules and glucosaminylmuramyl dipeptide (GMDP). Trea tment: GMDP [0.01-100 mu g/ml] applied to cell cultures for 6-72 h and to the chick chorioallantoic membrane (CAM) for four days. Methods: A ngiogenic activity of GMDP in vivo was assessed using the CAM assay; H UVEC proliferation was measured by tritiated thymidine incorporation a nd cell cycle studies; cell surface antigen expression by indirect imm unofluorescence and flow cytometry; cell adhesion by quantification of [H-3]-thymidine labeled leukocyte adherence to HUVEC monolayers. Stat istical analysis was performed using one-way ANOVA and if necessary wa s followed by Duncan's multiple range test for variables. Results: GMD P induced [H-3]-thymidine incorporation in a concentration-and time-de pendent manner (p < 0.003) and significantly increased the proportion of cells in the S phase of the cell cycle (p < 0.03). It weakly augmen ted the expression of ICAM-1 and CD31 but not adhesion of leukocytes t o HUVEC monolayers GMDP was not angiogenic in the CAM assay. Conclusio ns: GMDP can modulate endothelial cell activity without the induction of angiogenesis in vivo which may have implications for its use as a t herapeutic agent.