GROα in the Fetomaternal and Amniotic Fluid Compartments During Pregnancy and Parturition

PROBLEM: The use of monoclonal antibodies for CD45RA and CD45RO antigens is important in defining maturational and functional stages on lymphocytes. METHOD: To characterize distribution of two isoforms of CD45 antigen CD45RA and CD45RO on CD3⁺, CD4⁺, CD8⁺ and CD56⁺ lymphocyte subsets from first trimester human decidua, two-color flow cytometry were used. RESULTS: In decidua, there were much higher levels of CD45RO^a+ and much lower levels of CD45RA⁺ cells among CD3⁺, CD4⁺, and CD8⁺ cells as compared with peripheral blood samples of the same pregnant women. Only ?40% of CD56⁺ cells in decidua expressed CD45RA. Unlike peripheral blood, ?30% of decidual natural killer (NK) cells weakly stained with anti-CD45RO antibodies. Double-negative CD45RA^? CD45RO^? NK cells were also present in decidua. CONCLUSIONS: The significantly raised percentage of intradecidual T cells expressing CD45RO suggest decidual accumulation of antigen-committed memory cells. The patterns of CD45 isoforms expression on decidual CD56⁺ cells are consistent with hypothesis that uterine CD56⁺ lymphocytes are terminally differentiated cells of NK lineage. PROBLEM: GROα/MGSA is a new member of the chemokine superfamily CXC(α) and is produced by a variety of cells including macrophages, fibroblasts, epithelial, and endothelial cells, and keratinocytes. This chemokine has chemoattractant activity and may participate in neutrophil recruitment and activation during the course of intrauterine infection. This study was conducted to investigate the effect of labor and microbial invasion of the amniotic cavity (MIAC) on amniotic fluid, fetal, and maternal plasma GROα concentrations. METHOD: A cross-sectional study was designed using parameters that included gestational age, results of amniotic fluid (AF) cultures, and labor status at the time of amniocentesis. Fluid was retrieved by transabdominal amniocentesis. MIAC was defined as a positive amniotic fluid culture for bacteria. Umbilical cord blood was retrieved at the time of delivery. Amniotic fluid, maternal and fetal plasma GROα concentrations were measured with a sensitive and specific ELISA (Quantikine, R&D Systems, Minneapolis, MN). RESULTS: 1) GROα was detectable in amniotic fluid, umbilical cord, and maternal plasma samples; 2) GROα concentrations in amniotic fluid increased with advancing gestational age; 3) Both term and preterm gestations with MIAC were associated with higher amniotic fluid GROα concentrations than those with sterile amniotic fluid, independent of the labor status (term, MIAC, labor: median 2.7 ng/ml, range 1.4–12.7 vs. term, no MIAC, labor: median 2.1 ng/ml, range 0.7-3.4, vs term, no MIAC, no labor: median 1.9 ng/ml, range 1.8-4.2; P <0.005; preterm: MIAC median 5 ng/ml, range 0.6–47.9 vs. no MIAC: median 2.3 ng/ml, range 0.5–10; P <0.008); 4) A strong correlation was found between umbilical cord plasma GROα concentrations and neonatal neutrophil count, and between GROα concentrations and white blood cell count in the amniotic fluid (r = 0.67, P < 0.0005 and r ? 0.38, P < 0.001, respectively). CONCLUSION: GROα is a physiologic constituent of amniotic fluid and cord blood. Amniotic fluid GROα concentrations increase with gestational age. Intrauterine infection both preterm and at term is associated with an increase in GROα concentrations of amniotic fluid, suggesting that GROα may play an important role in recruitment of neutrophils into the amniotic cavity.