Bacterial lipopolysaccharide inhibits VEGFR2 expression and cell migration in fetal mouse lung mesenchyme (540.1)

Abstract

Infection and inflammation inhibit normal lung development. We have previously measured multiple alterations in growth factor expression and signaling that may link inflammation with abnormal development. Here we report data investigating the effects of the bacterial endotoxin lipopolysaccharide (LPS) on developmental gene expression in fetal mouse lung mesenchyme. Three separate mesenchymal cell lines were established from the embryonal lungs of ImmortoMice at E11, E15, and E18. We used these lines to measure persistent changes in gene expression (using Affymetrix MoGene 1.0st arrays) following LPS treatment. While each line showed similar acute inflammatory responses to LPS, only a small subset of 285 genes was down regulated. Further analysis identified a smaller set of 9 genes that consistently decreased in all lines tested, including the VEGF receptor VEGFR2. While mesenchymal cells can transdifferentiate into endothelial cells, they also migrate along newly formed blood vessels to form vascular pericytes. Treating mesenchymal cells with LPS reduced VEGF‐induced cell migration, but did not decrease the response to PDGF. These data suggest that persistent inflammation may alter mesenchymal cell biology in the developing lung by altering normal VEGFR2 expression and disrupting the spatial and temporal relationships required for normal alveolar capillary formation.