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Published in: BMC Pregnancy and Childbirth 1/2017

Open Access 01-12-2017 | Research article

Pregnant human peripheral leukocyte migration during several late pregnancy clinical conditions: a cross-sectional observational study

Authors: Jun Takeda, Xin Fang, David M. Olson

Published in: BMC Pregnancy and Childbirth | Issue 1/2017

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Abstract

Background

Parturition at term and preterm is characterized by sterile inflammatory processes occurring in the absence of infection whereby peripheral leukocytes infiltrate gestational tissues in response to chemotactic signals. In response to a homing signal, recruited leukocytes undergo diapedesis and extravasate through capillaries, migrating into stromal tissue. There they interact with resident immune and stromal cells to produce a mixture of matrix metalloproteinases, prostaglandins and cytokines including interleukin-1β (IL-1β) and IL-6 that in turn transform the uterus from pregnancy to parturition. Since migration is an early parturitional event our purpose was to study the migration of maternal peripheral blood leukocytes in response to a standard chemotactic signal during several different conditions of late pregnancy.

Methods

We used a cross-sectional observational study design. Subjects were (sTL) spontaneous normal labour delivered vaginally at term, (TNL) elective caesarean section at term without labour, (PTL) preterm in labour, (PTNL) preterm not in labour, (TPTL) threatened preterm labour, and (pPROM) preterm with premature rupture of membranes. Leukocytes (100,000) obtained by venipuncture and chemotactic factor isolated from term labour fetal membranes were placed in the upper and lower halves, respectively, of a Boyden chamber separated by a filter with 3μm pores. Migrated leukocytes were assessed by flow cytometry. The number of leukocytes that migrated in 90 min was the primary outcome measure.

Results

Increased numbers of leukocytes from peripheral blood of women in labour (TL or PTL) or soon to go into labour (PPROM) migrated towards a chemotactic signal than did leukocytes from women not in labour (TNL, PTNL, or TPTL) (p < 0.0001). All pPROM delivered within 7d; TPTL delivered >30d. Receiver operating characteristic curve parameters indicated the cut-off point for delivery within 7d to be 37,082 leukocytes with sensitivity 78.1%, specificity 88.9%, positive predictive value 91.4%, negative predictive value 72.7%, and area under the curve 0.83.

Conclusion

Leukocyte migration to a fetal membrane signal varies in a predictable fashion during various clinical situations of late gestation. This principle has the potential to be improved to become a clinical test to predict delivery.
Literature
1.
go back to reference Bokstrom H, Brannstrom M, Alexandersson M, Norstrom A. Leukocyte subpopulations in the human uterine cervical stroma at early and term pregnancy. Hum Reprod. 1997;12(1):586–90.CrossRefPubMed Bokstrom H, Brannstrom M, Alexandersson M, Norstrom A. Leukocyte subpopulations in the human uterine cervical stroma at early and term pregnancy. Hum Reprod. 1997;12(1):586–90.CrossRefPubMed
2.
go back to reference Osman I, Young A, Ledingham MA, Thomson AJ, Jordan F, Greer IA, Norman JE. Leukocyte density and pro-inflammatory cytokine expression in human fetal membranes, decidua, cervix and myometrium before and during labour at term. Mol Hum Reprod. 2003;9:41–5.CrossRefPubMed Osman I, Young A, Ledingham MA, Thomson AJ, Jordan F, Greer IA, Norman JE. Leukocyte density and pro-inflammatory cytokine expression in human fetal membranes, decidua, cervix and myometrium before and during labour at term. Mol Hum Reprod. 2003;9:41–5.CrossRefPubMed
3.
go back to reference Thomson AJ, Telfer JF, Young A, Campbell S, Stewart CJ, Cameron IT, Greer IA, Norman JE. Leukocytes infiltrate the myometrium during human parturition: further evidence that labour is an inflammatory process. Hum Reprod. 1999;14:229–36.CrossRefPubMed Thomson AJ, Telfer JF, Young A, Campbell S, Stewart CJ, Cameron IT, Greer IA, Norman JE. Leukocytes infiltrate the myometrium during human parturition: further evidence that labour is an inflammatory process. Hum Reprod. 1999;14:229–36.CrossRefPubMed
4.
go back to reference Ledingham MA, Thomson AJ, Jordan F, Young A, Crawford M, Norman JE. Cell adhesion molecule expression in the cervix and myometrium during pregnancy and parturition. Obstet Gynecol. 2001;97:235–42.PubMed Ledingham MA, Thomson AJ, Jordan F, Young A, Crawford M, Norman JE. Cell adhesion molecule expression in the cervix and myometrium during pregnancy and parturition. Obstet Gynecol. 2001;97:235–42.PubMed
5.
go back to reference Romero R, Espinoza J, Goncalves LF, Kusanovic JP, Friel LA, Nien JK. Inflammation in preterm and term labour and delivery. Semin Fetal Neonatal Med. 2006;11:317–26.CrossRefPubMed Romero R, Espinoza J, Goncalves LF, Kusanovic JP, Friel LA, Nien JK. Inflammation in preterm and term labour and delivery. Semin Fetal Neonatal Med. 2006;11:317–26.CrossRefPubMed
6.
go back to reference Winkler M, Kemp B, Fischer DC, Ruck P, Rath W. Expression of adhesion molecules in the lower uterine segment during term and preterm parturition. Microsc Res Tech. 2003;60:430–44.CrossRefPubMed Winkler M, Kemp B, Fischer DC, Ruck P, Rath W. Expression of adhesion molecules in the lower uterine segment during term and preterm parturition. Microsc Res Tech. 2003;60:430–44.CrossRefPubMed
7.
go back to reference Bollopragada S, Youssef R, Jordan F, Greer I, Norman J, Nelson S. Term labor is associated with a core inflammatory response in human fetal membranes, myometrium, and cervix. Am J Obstet Gynecol. 2009;200(1):104. e1-11.CrossRefPubMed Bollopragada S, Youssef R, Jordan F, Greer I, Norman J, Nelson S. Term labor is associated with a core inflammatory response in human fetal membranes, myometrium, and cervix. Am J Obstet Gynecol. 2009;200(1):104. e1-11.CrossRefPubMed
8.
go back to reference Young A, Thomson AJ, Ledingham M, Jordan F, Greer IA, Norman JE. Immunolocalization of proinflammatory cytokines in myometrium, cervix, and fetal membranes during human parturition at term. Biol Reprod. 2002;66(2):445–9.CrossRefPubMed Young A, Thomson AJ, Ledingham M, Jordan F, Greer IA, Norman JE. Immunolocalization of proinflammatory cytokines in myometrium, cervix, and fetal membranes during human parturition at term. Biol Reprod. 2002;66(2):445–9.CrossRefPubMed
9.
go back to reference Gomez-Lopez N, Estrada-Gutierrez G, Jiminez-Zamudio L, Vega-Sanchez R, Vadillo-Ortega F. Fetal membranes exhibit selective leukocyte chemotaxic activity during human labor. J Reprod Immunol. 2009;80(1-2):122–31.CrossRefPubMed Gomez-Lopez N, Estrada-Gutierrez G, Jiminez-Zamudio L, Vega-Sanchez R, Vadillo-Ortega F. Fetal membranes exhibit selective leukocyte chemotaxic activity during human labor. J Reprod Immunol. 2009;80(1-2):122–31.CrossRefPubMed
10.
go back to reference Gomez-Lopez N, Vadillo-Perez L, Nessim S, Olson DM, Vadillo-Ortega F. Choriodecidua and amnion exhibit selective chemotaxis during term labor. Am J Obstet GynecolAmerican. 2011;204(4):364. e9-364.e16. Gomez-Lopez N, Vadillo-Perez L, Nessim S, Olson DM, Vadillo-Ortega F. Choriodecidua and amnion exhibit selective chemotaxis during term labor. Am J Obstet GynecolAmerican. 2011;204(4):364. e9-364.e16.
11.
go back to reference Chang JR, Tees DFJ, Hammer DA. The state diagram for cell adhesion under flow: leukocyte rolling and firm adhesion. Proc Natl Acad Sci. 2000;97(1):11262–7.CrossRefPubMedPubMedCentral Chang JR, Tees DFJ, Hammer DA. The state diagram for cell adhesion under flow: leukocyte rolling and firm adhesion. Proc Natl Acad Sci. 2000;97(1):11262–7.CrossRefPubMedPubMedCentral
12.
go back to reference Challis JR, Lockwood CJ, Myatt L, Norman JE, Strauss 3rd JF, Petraglia F. Inflammation and pregnancy. Reprod Sci. 2009;16(2):206–15.CrossRefPubMed Challis JR, Lockwood CJ, Myatt L, Norman JE, Strauss 3rd JF, Petraglia F. Inflammation and pregnancy. Reprod Sci. 2009;16(2):206–15.CrossRefPubMed
13.
go back to reference Myatt L, Sun K. Role of fetal membranes in signalling of fetal maturation and parturition. Int J Dev Biol. 2010;54(2-3):545–53.CrossRefPubMed Myatt L, Sun K. Role of fetal membranes in signalling of fetal maturation and parturition. Int J Dev Biol. 2010;54(2-3):545–53.CrossRefPubMed
14.
go back to reference Gomez-Lopez N, Tanaka S, Zaeem Z, Metz GA, Olson DM. Maternal circulating leukocytes display early chemotactic responsiveness during late gestation. BMC Pregnancy Childbirth. 2013;13 Suppl 1:S8.CrossRefPubMedPubMedCentral Gomez-Lopez N, Tanaka S, Zaeem Z, Metz GA, Olson DM. Maternal circulating leukocytes display early chemotactic responsiveness during late gestation. BMC Pregnancy Childbirth. 2013;13 Suppl 1:S8.CrossRefPubMedPubMedCentral
15.
go back to reference Gomez-Lopez N, Tong WCH, Arenas-Hernandez M, Tanaka S, Hajar O, Olson DM, Taggart MJ, Mitchell B. Chemotactic activity of gestational tissues through late pregnancy, term labor and RU486-induced preterm labor in guinea pigs. Am J Reprod Immunol. 2015;73(4):341–52.CrossRefPubMed Gomez-Lopez N, Tong WCH, Arenas-Hernandez M, Tanaka S, Hajar O, Olson DM, Taggart MJ, Mitchell B. Chemotactic activity of gestational tissues through late pregnancy, term labor and RU486-induced preterm labor in guinea pigs. Am J Reprod Immunol. 2015;73(4):341–52.CrossRefPubMed
16.
go back to reference Yuan M, Jordan F, McInnes IB, Harnett MM, Norman JE. Leukocytes are primed in peripheral blood for activation during term and preterm labour. Mol Hum Reprod. 2009;15(11):713–24.CrossRefPubMedPubMedCentral Yuan M, Jordan F, McInnes IB, Harnett MM, Norman JE. Leukocytes are primed in peripheral blood for activation during term and preterm labour. Mol Hum Reprod. 2009;15(11):713–24.CrossRefPubMedPubMedCentral
18.
go back to reference Cooper S, Lange I, Wood S, Tang S, Miller L, Ross S. Diagnostic accuracy of rapid phIGFBP-I assay for predicting preterm labor in symptomatic patients. J Perinatol. 2012;32(6):460–5.CrossRefPubMed Cooper S, Lange I, Wood S, Tang S, Miller L, Ross S. Diagnostic accuracy of rapid phIGFBP-I assay for predicting preterm labor in symptomatic patients. J Perinatol. 2012;32(6):460–5.CrossRefPubMed
19.
go back to reference Sananes N, Langer B, Gaudineau A, Kutnahorsky R, Aissi G, Fritz G, Boudier E, Viville B, Nisand I, Favre R. Prediction of spontaneous preterm delivery in singleton pregnancies: Where are we and where are we going? A review of literature. J Obstet Gynaecol. 2014;34:457–61.CrossRefPubMed Sananes N, Langer B, Gaudineau A, Kutnahorsky R, Aissi G, Fritz G, Boudier E, Viville B, Nisand I, Favre R. Prediction of spontaneous preterm delivery in singleton pregnancies: Where are we and where are we going? A review of literature. J Obstet Gynaecol. 2014;34:457–61.CrossRefPubMed
Metadata
Title
Pregnant human peripheral leukocyte migration during several late pregnancy clinical conditions: a cross-sectional observational study
Authors
Jun Takeda
Xin Fang
David M. Olson
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Pregnancy and Childbirth / Issue 1/2017
Electronic ISSN: 1471-2393
DOI
https://doi.org/10.1186/s12884-016-1204-5

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