The factors responsible for the progression of disease from infection to clinical lymphedema remain undefined. Even though infected individuals appear asymptomatic, they exhibit subclinical manifestations including lymphangiectasia or dilated lymphatics. The parasite is thought to be responsible for alterations in the lymphatic endothelium since removal or killing of the worms reverses the dilation. Furthermore, lymphangiectasia is seen in SCID mice, arguing that the adaptive immune response is not the only driver of this lymphatic pathology. Lymphatic dilation is greatest near the site of the worm nest, but it is not restricted to the site of the worm nest and is found along the length of infected vessels suggesting that a soluble product secreted by the worm may be mediating these effects. These findings support the conclusion that the presence of living adult worms and their ES products alters LV tissue. Taken together, these Diisopropylammonium dichloroacetate observations suggest that LECs are the prime targets of parasite-derived factors which initiate the development of clinical pathology. We and others have previously characterized the protein constituents making up the filarial ES products released by the worm, but the biological effects of these molecules have not been fully elucidated. Given the altered pathology along the length of the infected vessel and intimate relationship between the parasite and the endothelial cells lining the LVs, worm ES products may be contributing to the pathogenesis of disease. Therefore, we examined the biological effects of filarial ES products on LECs. LECs were stimulated with filarial ES products and assayed for changes in differentiation, activation and proliferation. Changes in cell Mechlorethamine hydrochloride surface marker expression profiles, the presence of phosphorylated cell signaling molecules, gene expression and growth factor production were used to characterize the LEC response to worm ES products. The association of lymphangiectasia with the presence of active filarial infection argues that, soluble parasite factors may be mediating the effect in vivo. We originally hypothesized that the ES products of the worms were activating the lymphatic endothelium; however, we were not able to detect a direct effect of the ES products on the activation of LECs as summarized in Table 2. We considered that the lymphangiectasia could be due to an increase in the rate of LEC proliferation, but we did not see increased proliferation of these cells in repeated assays. In addition, the LECs did not appear to be stimulated by ES products as assessed by expression of cell surface molecules or production of growth factors or cytokines. The positive controls in these assays induced the expected responses, so the cells were viable and functional; however, the filarial ES products did not induce detectable responses by LECs.