Chemotactic Activity of Gestational Tissues Through Late Pregnancy, Term Labor, and <scp>RU</scp>486‐Induced Preterm Labor in Guinea Pigs

Gomez‐Lopez, Nardhy; Tong, Wing Chiu; Arenas‐Hernandez, Marcia; Tanaka, Satomi; Hajar, Omar; Olson, David M.; Taggart, Michael J.; Mitchell, Bryan F.

doi:10.1111/aji.12333

Cited by 21 publications

(21 citation statements)

References 47 publications

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“…This finding is in line with previous studies demonstrating that the chorioamniotic membranes (including the decidua) exhibit leukocyte chemotaxis through the expression of these chemokines during the process of labor [14,23,25,26]. These results suggest that besides being a source of pro-inflammatory mediators, the choriodecidual leukocytes can actively participate in the process of leukocyte recruitment during the process of labor.…”

Section: Resultssupporting

confidence: 92%

“…The current hypothesis is that the chorioamniotic membranes exhibit chemotactic processes driven by specific chemokines in order to recruit maternal circulating * Nardhy Gomez-Lopez nardhy.gomez-lopez@wayne.edu * Rodrigo Vega-Sanchez r.vega@inper.mx vegarodrig@gmail.com leukocytes into the choriodecidua [14,16,[23][24][25]. In addition, the responsiveness of peripheral leukocytes to be attracted to chemotactic stimuli derived from the chorioamniotic membranes seems to be a key feature in this process [26].…”

Section: Introductionmentioning

confidence: 99%

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Choriodecidual leukocytes display a unique gene expression signature in spontaneous labor at term

et al. 2018

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Prior to and during the process of human labor, maternal circulating leukocytes infiltrate the maternal-fetal interface (choriodecidua) and become activated resembling choriodecidual leukocytes. Since, there is no evidence comparing maternal circulating and choriodecidual leukocytes, herein, we characterized their transcriptome and explored the biological processes enriched in choriodecidual leukocytes. From women undergoing spontaneous term labor we isolated circulating and choriodecidual leukocytes, performed microarray analysis (n = 5) and qRT-PCR validation (n = 9) and interaction network analysis with up-regulated genes. We found 270 genes up-regulated and only 17 genes down-regulated in choriodecidual leukocytes compared to maternal circulating leukocytes. The most up-regulated genes were CCL18, GPNMB, SEPP1, FN1, RNASE1, SPP1, C1QC, and PLTP. The biological processes enriched in choriodecidual leukocytes were cell migration and regulation of immune response, chemotaxis, and humoral immune responses. Our results show striking differences between the transcriptome of choriodecidual and maternal circulating leukocytes. Choriodecidual leukocytes are enriched in immune mediators implicated in the spontaneous process of labor at term.

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Section: Resultssupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Choriodecidual leukocytes display a unique gene expression signature in spontaneous labor at term

et al. 2018

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“…Exclusion criteria were the same as for leukocyte collection. The preparation of the chemoattractant was as published with minor modifications [9, 10, 14, 15]. From each of the fifteen sets of fetal membranes a 4cm square piece was cut.…”

Section: Methodsmentioning

confidence: 99%

“…The procedure used was published [9, 10, 14, 15] with recent modifications to improve the assay performance. Modified Boyden chemotaxis chambers (AP48; Neuro Probe, Gaithersburg, MD, USA) were used in the assay.…”

Section: Methodsmentioning

confidence: 99%

“…We demonstrated in rats and guinea pigs that the uterus or chorio-amnion produce increasing concentrations of chemotactic factor in late gestation, and there is an increase in leukocyte responsiveness to this factor [14, 15]. Full thickness fetal membranes (amnion, chorion, decidua vera) isolated from spontaneous term labour (TL) patients also is a significant source of chemoattractant of term leukocytes in biological assays [9, 10] and the chemoattractive potency of TL fetal membrane extract is greater than extract obtained from term not in labour patients (TNL).…”

Section: Introductionmentioning

confidence: 99%

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

Takeda

Fang

Olson

2017

BMC Pregnancy Childbirth

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BackgroundParturition 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.MethodsWe 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.ResultsIncreased 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.ConclusionLeukocyte 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.

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Specific innate immune cells uptake fetal antigen and display homeostatic phenotypes in the maternal circulation

Arenas‐Hernandez

Romero

Gershater

et al. 2021

Journal of Leukocyte Biology

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Pregnancy represents a period when the mother undergoes significant immunological changes to promote tolerance of the fetal semi‐allograft. Such tolerance results from the exposure of the maternal immune system to fetal antigens (Ags), a process that has been widely investigated at the maternal‐fetal interface and in the adjacent draining lymph nodes. However, the peripheral mechanisms of maternal‐fetal crosstalk are poorly understood. Herein, we hypothesized that specific innate immune cells interact with fetal Ags in the maternal circulation. To test this hypothesis, a mouse model was utilized in which transgenic male mice expressing the chicken ovalbumin (OVA) Ag under the beta‐actin promoter were allogeneically mated with wild‐type females to allow for tracking of the fetal Ag. Fetal Ag‐carrying Ly6G+ and F4/80+ cells were identified in the maternal circulation, where they were more abundant in the second half of pregnancy. Such innate immune cells displayed unique phenotypes: while Ly6G+ cells expressed high levels of MHC‐II and CD80 together with low levels of pro‐inflammatory cytokines, F4/80+ cells up‐regulated the expression of CD86 as well as the anti‐inflammatory cytokines IL‐10 and TGF‐β. In vitro studies using allogeneic GFP+ placental particles revealed that maternal peripheral Ly6G+ and F4/80+ cells phagocytose fetal Ags in mid and late murine pregnancy. Importantly, cytotrophoblast‐derived particles were also engulfed in vitro by CD15+ and CD14+ cells from women in the second and third trimester, providing translational evidence that this process also occurs in humans. Collectively, this study demonstrates novel interactions between specific maternal circulating innate immune cells and fetal Ags, thereby shedding light on the systemic mechanisms of maternal‐fetal crosstalk.

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Chemotactic Activity of Gestational Tissues Through Late Pregnancy, Term Labor, and RU486‐Induced Preterm Labor in Guinea Pigs

Abstract: Leukocyte CA of intrauterine tissues is increased in term spontaneous labor. However, RU486-induced preterm labor occurs in the absence of increased CA.

Cited by 21 publications

References 47 publications

Choriodecidual leukocytes display a unique gene expression signature in spontaneous labor at term

Choriodecidual leukocytes display a unique gene expression signature in spontaneous labor at term

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

Specific innate immune cells uptake fetal antigen and display homeostatic phenotypes in the maternal circulation

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