ABSTRACT
Vascular endothelial growth factor (VEGF) signals on vascular and hematopoietic cells via its receptors, VEGFR-2 (KDR) and VEGFR-1 (FLT-1). Elevated levels of VEGF, such as during tumor growth or inflammation, have been suggested to suppress hematopoiesis; most studies refer to KDR as the main receptor involved in this inhibitory effect. In the present study, having detected expression of FLT-1 in B-lymphoid precursors, we exploited the possibility that VEGF signaling via FLT-1 might affect early B-cell commitment. Using a well-established in vitro B-cell differentiation assay, we demonstrate that FLT-1 blockade promotes B-cell commitment and subsequent differentiation, while KDR blockade has no effect on B-cell commitment. In agreement, in vivo transplantation of human (CD34+) or murine (Sca1+l/Lin-) FLT-1-negative hematopoietic precursors into irradiated severe combined immune-deficient mice restored the bone marrow lymphoid compartment, while transplanting the FLT-1-positive counterpart failed to repopulate the lymphoid compartment, and unexpectedly resulted in early death of the irradiated recipients due to hematopoietic suppression. Taken together, we suggest that VEGF signaling via FLT-1 on hematopoietic precursors may restrict lymphopoiesis.
Subject(s)
B-Lymphocytes/immunology , B-Lymphocytes/transplantation , Vascular Endothelial Growth Factor A/physiology , Animals , B-Lymphocytes/cytology , Bone Marrow Cells/immunology , Cell Differentiation , Humans , Mice , Placenta Growth Factor , Pregnancy Proteins/genetics , Pregnancy Proteins/physiology , RNA/genetics , RNA/isolation & purification , Receptors, Vascular Endothelial Growth Factor/immunology , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor Receptor-2/immunologyABSTRACT
OBJECTIVE: The aim of our study is to evaluate the clinical importance of near term weight discordance in twin pregnancies with both appropriate or with one small for gestational age newborn (AGA and SGA, respectively). METHODS: We retrospectively studied 230 twin pregnancies that ended at >or=34 weeks' gestation. Discordance was defined as an intertwin birth weight difference>or=20% calculated from the heavier newborn. The following data were compared between discordant and concordant pairs: maternal age, parity, mode of conception, placentation, hypertensive disorders of pregnancy, gestational age at birth, route of delivery, reason for termination of pregnancy, Apgar scores, birth weights, admission to neonatal intensive care unit, significant morbidity, malformations found at birth, and perinatal mortality. The discordant pairs were subdivided into two groups: (1) Both twins were AGA; (2) One of the twins was SGA. The two groups were compared to each other, and to the control group of concordant pairs. RESULTS: One hundred and seventy-six twin pairs were concordant (control group) and 54 were discordant. The comparison between the concordant and the discordant groups did not show statistically significant differences in any of the examined parameters. However, the discordant group had a greater incidence of neonatal morbidity. When the discordant subgroups (AGA, n=24 vs. SGA n=30) were compared to the concordant group, these differences persist, particularly in the SGA group. CONCLUSION: In near term twin pregnancies, birth weight discordance does not seem to predict adverse perinatal outcome except when one of the newborns is SGA.
