Abstract-Neutrophil activation and increased migration is associated with preeclampsia and is resolved after delivery.Preeclampsia is an inflammatory disorder where altered levels of vascular endothelial growth factor (VEGF) and the circulating soluble fms-like tyrosine kinase 1 (sFlt-1) have a pathogenic role. VEGF, by binding to FLT-1, induces leukocytic chemotaxis. We studied expression and function of FLT-1 in maternal neutrophils during preeclampsia and normal pregnancies. Analysis of maternal neutrophils showed the relationship between FLT-1 expression and week of gestation. Preeclamptic women express lower FLT-1 and sFLT-1 in neutrophils. In contrast, serum levels of sFLT-1 in patients with preeclampsia are increased and, therefore, inhibit upregulation of FLT-1 in neutrophils by neutralizing VEGF. VEGF-dependent FLT-1 expression is regulated by changing FLT-1-promoter activity. Promoter activity is decreased by sFLT-1. In vitro experiments demonstrated that migration of neutrophils is regulated by VEGF via FLT-1 and excess of sFLT-1. Thus, VEGF-dependent migration of neutrophils is decreased during preeclampsia as a consequence of excess circulating sFlt1. But, they still increase migration by fMLP and, therefore, migration of neutrophils from preeclamptic women is highly activated when compared with the normotensive group. In conclusion, besides being involved in inducing an antiangiogenic state in the serum, excess of sFLT-1 seems to prevent activated neutrophils from women with preeclampsia from additional migration by VEGF. We provide evidence that neutrophils may be involved in the pathophysiology of pregnancy-related hypertensive disorders. Key Words: migration Ⅲ neutrophils Ⅲ preeclampsia Ⅲ pregnancy Ⅲ VEGF receptor 1 P reeclampsia (PE) is a hypertensive disorder of unknown etiology affecting 5% to 10% of all pregnancies. Pathophysological changes include elevated systemic vascular resistance, generalized vasoconstriction, activation of the coagulation cascade, maternal endothelial dysfunction, and a poorly perfused fetoplacental unit. 1 Preeclampsia is characterized by altered cytokine production 2 and marked neutrophil activation. 3-6 They release proteases and reactive oxygen species, which can cause vascular endothelial injury, inappropriate endothelial activation or transformation. 7-9 The latter processes are important for physiological adaptations during normal pregnancy creating a low-resistance arteriolar system, which allows adequate blood supply to the growing fetus. 10,11 Recently, case-control studies have shown associations between polymorphisms of the vascular endothelial growth factor (VEGF) gene and preeclampsia. 12 VEGF is a multifunctional cytokine that plays a pivotal role in angiogenesis in vivo. 13 VEGF is expressed by different cells, eg, smooth muscle, endothelial cells, monocytes/macrophages, and polymorphonuclear neutrophils (PMNs). VEGF exerts its biological effects through Fms-like tyrosine kinase 1 (FLT-1)/ VEGF receptor-1 and VEGF receptor-2 (FLK-1/KDR). 13 KDR is con...