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Titolo:
Activation of the novel prothrombinase, fgl2, as a basis for the pregnancycomplications spontaneous abortion and pre-eclampsia
Autore:
Knackstedt, M; Ding, JW; Arck, PC; Hertwig, K; Coulam, CB; August, C; Lea, R; Dudenhausen, JW; Gorczynski, RM; Levy, GA; Clark, DA;
Indirizzi:
McMaster Univ, Dept Med, Hamilton, ON L8N 3Z5, Canada McMaster Univ Hamilton ON Canada L8N 3Z5 ed, Hamilton, ON L8N 3Z5, Canada McMaster Univ, Dept Mol Med, Hamilton, ON L8N3Z5, Canada McMaster Univ Hamilton ON Canada L8N3Z5 Med, Hamilton, ON L8N3Z5, Canada McMaster Univ, Dept Pathol, Hamilton, ON L8N3Z5, Canada McMaster Univ Hamilton ON Canada L8N3Z5 thol, Hamilton, ON L8N3Z5, Canada McMaster Univ, Dept Obstet, Hamilton, ON L8N3Z5, Canada McMaster Univ Hamilton ON Canada L8N3Z5 stet, Hamilton, ON L8N3Z5, Canada McMaster Univ, Dept Gynecol, Hamilton, ON L8N3Z5, Canada McMaster Univ Hamilton ON Canada L8N3Z5 ecol, Hamilton, ON L8N3Z5, Canada Univ Toronto, Res Inst, Toronto Gen Hosp, CIHR Grp Organ Injury, Toronto, ON, Canada Univ Toronto Toronto ON Canada IHR Grp Organ Injury, Toronto, ON, Canada Humboldt Univ, Berlin, Germany Humboldt Univ Berlin GermanyHumboldt Univ, Berlin, Germany Humboldt Univ, Dept Obstet & Gynaecol, Berlin, Germany Humboldt Univ Berlin Germany v, Dept Obstet & Gynaecol, Berlin, Germany Sher Inst, Chicago, IL USA Sher Inst Chicago IL USASher Inst, Chicago, IL USA Illinois Masonic Hosp, Dept Pathol, Chicago, IL USA Illinois Masonic HospChicago IL USA Hosp, Dept Pathol, Chicago, IL USA Rowett Res Inst, Bucksburn AB2 9SB, Aberdeen, Scotland Rowett Res Inst Bucksburn Aberdeen Scotland AB2 9SB B, Aberdeen, Scotland
Titolo Testata:
AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
fascicolo: 3, volume: 46, anno: 2001,
pagine: 196 - 210
SICI:
1046-7408(200109)46:3<196:AOTNPF>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
FETAL GROWTH-RETARDATION; EARLY-ONSET PREECLAMPSIA; X DBA/2 MICE; HUMAN CYTOTROPHOBLASTS; ENDOVASCULAR INVASION; PROCOAGULANT FGL2; HUMAN PLACENTA; IN-VITRO; WOMEN; TROPHOBLAST;
Keywords:
pre-eclampsia; pregnancy immunology; prothrombinase; spontaneous abortion;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
63
Recensione:
Indirizzi per estratti:
Indirizzo: Clark, DA McMaster Univ, Dept Med, Rm 3V39,1200 Main St, Hamilton, ON L8N 3Z5, Canada McMaster Univ Rm 3V39,1200 Main St Hamilton ON Canada L8N 3Z5 da
Citazione:
M. Knackstedt et al., "Activation of the novel prothrombinase, fgl2, as a basis for the pregnancycomplications spontaneous abortion and pre-eclampsia", AM J REPROD, 46(3), 2001, pp. 196-210

Abstract

PROBLEM: Impaired trophoblast invasion during the first trimester of pregnancy is linked to spontaneous abortion, and defective invasion in the second trimester to hypertension + proteinuria (pre-eclampsia). Hypertension developing during the third trimester of human pregnancy represents, in part, a corrective response in the mother to provide adequate placental perfusionfor fetal growth when trophoblast has not to invaded and converted the myometrial porprtion of maternal spiral arteries into to low resistance-high capacitance conduits. Deportation of vesicles from hypoxemic trophoblast is thought to cause hypertension plus proteinuria, vascular damage and a systemic coagulopathy. Trophoblast invasion may be inhibited by local cytokines,such as TGF-beta but Th1-type cytokines associated with pre-eclapmsia and spontaneous abortions (e.g., IL-1, TNF-alpha, IFN-gamma) are not known to inhibit migration at in situ concentrations. Trophoblast invasion is also inhibited by the binding of surface integrins to fibronectin and fibrin, and fibrin production is stimulated by these Th1. cytokines via up-regulation of prothrombinases(s) such as fgl2 which directly and via TNF-alpha -facilitated inflamation compromise trophoblast cell integrity. We, therefore, asked if fgl2 expression and TNF-alpha are increased in first trimester human miscarriage and in third trimester pre-eclampsia. METHODS: fgl2 mRNA was detected using in situ hybridization and fgl2 protein by immunohistochemistry. TNF-alpha mRNA and protein were similarly tested. The techniques were validated using uterine sections from day 8.5 of CBAx DBA/2 pregnancies, and then were applied to sections of placentae from normal and pre-eclamptic pregnancies with and without intrauterine fetal growth restriction (IUGR). Fibrin was detectectd by immunohistochemistry. RESULTS: Expression of fgl2 protein correlated with fgl2 mRNA expression in mouse uteri and in placentae from normal human pregnancies. Increased expression of fgl2 and TNF-alpha mRNA and protein, and increased fibrin deposition was detected in placental trophoblast. CONCLUSIONS: Activation of fgl2 prothrombinase by Th1-type cytokines in pregnancy may lead to spontaneous abortion, or in ongoing pregnancy, to pre-eclampsia and/or IUGR.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/09/20 alle ore 10:50:52