title: Mechanisms of abruption-induced premature rupture of the fetal membranes: thrombin-enhanced interleukin-8 expression in term decidua.
abstract: 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.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, 333 Cedar St., PO Box 208063, Room 334FMB, New Haven, CT 06520-8063, USA. chairobgyn@yale.edu
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Lockwood
authors.forename: Paolo
authors.initials: P
authors.lastname: Toti
authors.forename: Felice
authors.initials: F
authors.lastname: Arcuri
authors.forename: Michael
authors.initials: M
authors.lastname: Paidas
authors.forename: Lynn
authors.initials: L
authors.lastname: Buchwalder
authors.forename: Graciela
authors.initials: G
authors.lastname: Krikun
authors.forename: Frederick
authors.initials: F
authors.lastname: Schatz
mesh_terms: D000037:Abruptio Placentae / Q000473:pathology / Q000503:physiopathology*; D000328:Adult; D015153:Blotting, Western; D002478:Cells, Cultured; D003656:Decidua / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000209:etiology*; D005337:Fibrin / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000096:biosynthesis*; D016256:Lewis X Antigen / Q000032:analysis; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000502:physiology; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013917:Thrombin / Q000502:physiology*
chemical_list: D016209:Interleukin-8; D016256:Lewis X Antigen; D012333:RNA, Messenger; D004958:Estradiol; D005337:Fibrin; D017258:Medroxyprogesterone Acetate; D013917:Thrombin