Mouse anti-Human SRGN monoclonal antibody, clone 2E9

uNK cells differ from cNK cells, as they produce angiogenic molecules critical for normal implantation site development. We evaluated heterogeneity among DBA(+)uNK cells for Prf, Gzma, and Vegfa. Ctsd and Srgn expression was used to assign intracellular sorting of these molecules on gd7, -9, and -14. Vegfa was present in small, granule-free DBA(+)uNK cells at gd7 and in large, granule-rich DBA(+)uNK cells at gd9 and -14. Prf and Gzma were only found in granulated DBA(+)uNK cells (gd9 and -14). All granule-rich Prf(+)DBA(+)uNK cells appeared to coexpress Vegfa. Thus, all DBA(+)uNK cells were Vegfa-producing cells. PC analysis and immuno-gold ultrastructure confirmed colocalization of Prf/Ctsd in secretory-lysosome granules (PC>0.5). Surprisingly, Gzma and Prf(+)Ctsd(+) were not colocalized (PC<0.5). Rather, Gzma colocalized with Srgn (PC>0.5) in small granules in cells with Vegfa expression (PC<0.5). NK1.1(+)sNK cells and DBA(+)uNK cells expressed genes regulating vesicular traffic (rab11, rab27a, snap23, vamp7), but uNK cells also expressed rab34 and vamp8, molecules associated with constitutive secretion. SEE activated the regulated secretory pathway of DBA(+)uNK cells in vivo, mobilizing Prf and Gzma but not Vegfa. Thus, DBA(+)uNK cells display constitutive and regulated secretion. Further, these results demonstrate that granule-free DBA(+)uNK cells are not quiescent immature cells, but they are cells with potentially significant angiogenic roles before and in addition to their initiation of spiral arterial remodeling. J. Leukoc. Biol. 92: 195-204; 2012.

Objective: To test several key glucocorticoid genes that are enhanced in lung development for associations with respiratory distress syndrome (RDS) after antenatal corticosteroid use. Methods: A prospective cohort of women received betamethasone to accelerate fetal lung maturity for threatened preterm delivery. DNA was obtained from mothers and newborns. Neonatal RDS was the primary outcome. Genotyping for single-nucleotide polymorphisms (SNPs) in 68 glucocorticoid genes found to be differentially expressed during lung development was performed. Multivariable analysis tested for associations of SNPs in the candidate genes with RDS. Results: Genotypic results for 867 SNPs in 96 mothers and 73 babies were included. Thirty-nine (53.4%) babies developed RDS. Maternal SNPs in the centromeric protein E (CENPE), GLRX, CD9, and AURKA genes provided evidence of association with RDS (P < .01). In newborns, SNPs in COL4A3, BHLHE40, and SRGN provided evidence of association with RDS (P < .01). Conclusion: Single-nucleotide polymorphisms in several glucocorticoid responsive genes suggest association with neonatal RDS after antenatal corticosteroid use.