Oral or Poster Presentation
Concurrent Session 3B - Maternal Fetal Medicine
Introduction: Enhanced Leukocyte Chemotaxis (ELC) occurs when circulating maternal leukocytes increase their migration towards chemotactic factors from the uterus. We showed that ELC occurs at term (TL) and preterm labour (PL) in mice and it predicts spontaneous term delivery in pregnant women. Here we identify key chemotaxis receptors and intracellular signalling molecules of ELC at human TL and PL.
Methods: Fetal membranes were collected at PL (n=3) and TL (n=6) to prepare whole tissue extracts at 100 mg/mL in DMEM-F12. Leukocytes were isolated by sedimentation of erythrocytes from whole blood at preterm not-in-labour (PNL; n=9), PL (n=5), term not-in-labour (TNL; n=8) and TL (n=6) and then assessed for chemotactic activity using a Boyden Chamber. Whole blood RNA was used to assess the abundance of CXCR1-5, CCR1-8, CX3CR1, PI3KCA/B/D/G, RAC1, RHOA, CDC42, VAV1, ARP2 and ARP3 relative to ACTB. The chemotaxis of TL leukocytes towards TL extracts was assessed in the presence of SB225002 or J113863, CXCR2 and CCR1 antagonists, respectively. PL leukocyte chemotaxis towards PL extracts was assessed in the presence of JMS17-HCl, a CX3CR1 antagonist. Correlations were explored by Pearson’s correlation test and statistical differences were determined by ANOVA (p<0.05).
Results: Term leukocyte chemotaxis towards TL extracts was positively correlated with expression of CXCR2, CXCR3, CXCR5, CCR1, CCR3, CCR5, CCR7, PI3KCB, PI3KCD, RAC1, VAV1, ARP2 and ARP3 (p<0.05-0.0001) and negatively correlated with CCR4 (p<0.05). SB225002 or J113863 treatment caused a dose-dependent reduction in TL leukocyte chemotaxis towards TL extracts (p<0.05-0.001). CX3CR expression was significantly higher at PL than PNL (p<0.01); inhibition of CX3CR1 caused reduced PL leukocyte chemotaxis towards PL extracts (p<0.05).
Conclusion: Fourteen term ELC chemotaxis-associated proteins and one preterm ELC were identified. This key distinction may guide development of predictive tools for term and preterm delivery.