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(American Journal of Pathology. 2005;167:1443-1449.)
© 2005 American Society for Investigative Pathology

Mechanisms of Abruption-Induced Premature Rupture of the Fetal Membranes

Thrombin-Enhanced Interleukin-8 Expression in Term Decidua

Charles J. Lockwood^*, Paolo Toti, Felice Arcuri, Michael Paidas^*, Lynn Buchwalder^*, Graciela Krikun^* and Frederick Schatz^*

From the Department of Obstetrics, Gynecology, and Reproductive Sciences,^* Yale University School of Medicine, New Haven, Connecticut; and the Institute of Pathological Anatomy and Histology, University of Siena, Siena, Italy

Recent evidence has linked preterm premature rupture of the fetal membranes (PPROM) to placental abruption. Because neutrophils are a rich source of proteases that can degrade extracellular matrix in abruption-associated PPROM, we examined whether decidual neutrophil infiltration complicates abruption-associated PPROM. Accordingly, immunostaining for the neutrophil marker CD15 was performed in placentas obtained after overt abruption (decidual hemorrhage) with or without PPROM and in control placentas. Abruptions were associated with a marked decidual neutrophil infiltration that peaked after PPROM, whereas decidua from gestational age-matched controls were virtually devoid of neutrophils. Neutrophil infiltrates co-localized with fibrin deposition. Because abruptions elicit intense decidua-enhanced thrombin production, we examined the regulation of abruption-induced neutrophil infiltration. Expression of the primary neutrophil chemoattractant interleukin-8 (IL-8) was evaluated in leukocyte-free term decidual cells incubated with estradiol (E₂; control) or with E₂ + medroxyprogesterone acetate (to mimic pregnancy) ± thrombin. After 24 hours, enzyme-linked immunosorbent assay measurements indicated that thrombin (0.1 to 2.5 U/ml) elicited a dose-dependent elevation in secreted IL-8 (P < 0.05) with 2.5 U/ml of thrombin increasing IL-8 levels by >14-fold in E₂ and E₂ + medroxyprogesterone incubations. Results were validated by Western blot and quantitative reverse transcriptase-polymerase chain reaction. In summary, thrombin-enhanced IL-8 expression in term decidual cells may explain how abruption-associated PPROM promotes decidual neutrophil infiltration.

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