Phenotypic and metabolic characteristics of maternal monocytes and granulocytes in preterm labor with intact membranes

Wayne State University, Detroit, Michigan, United States
American Journal of Obstetrics and Gynecology (Impact Factor: 4.7). 11/2001; 185(5):1124-9. DOI: 10.1067/mob.2001.117681
Source: PubMed


Experimental and clinical studies support a role for the fetus in the control of the onset of labor. Fetal systemic inflammation, but not a maternal inflammatory response, has been linked to the onset of preterm labor and delivery on the basis of the determination of inflammatory cytokines in fetal and maternal blood. We propose that parturition requires fetomaternal cooperation and that inflammation is an integral part of the parturitional process. This study used flow cytometry, a sensitive technique for the detection of intravascular inflammation, to assess whether maternal inflammation is present in preterm labor.
A prospective cross-sectional study was performed including patients with preterm labor (n = 55) and women with normal pregnancy (n = 50). Intravascular inflammation was studied by using flow cytometry. Maternal blood was assayed to determine granulocyte and monocyte phenotype by using monoclonal antibodies, which included the following cluster of differentiation (CD) markers: CD11b, CD14, CD15, CD16, CD18, CD49d, CD62L, CD64, CD66b, and HLA-DR. Oxidative burst and generation of basal intracellular oxygen radical species were assessed. Statistical analysis was conducted with the use of nonparametric methods. A P value of <.01 was considered statistically significant.
Preterm labor was associated with a significant increase in the median mean channel brightness of CD11b, CD15, and CD66b on granulocytes and median mean channel brightness of CD11b and CD15 on monocytes. The ratio of oxidative burst over basal intracellular oxygen radical species in both granulocytes and monocytes was increased in preterm labor (P <. 01).
Preterm labor with intact membranes is associated with phenotypic and metabolic changes of maternal granulocytes and monocytes.

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    • "Thus, the differential expression of infection- or inflammation-related genes in our study could be attributed to a combination of infection and labor. For example, inflammatory-related genes and their respective proteins such as NFKB1 [48], CCR1 [49], SOCS3, JAK3 [50], JUNB [51], RHOG [52], TIMP1 [53], IL1beta [54]–[57], ITGAM [58], CD44 [59], [60], TLR5 [61]–[63] and CXCR1 [64], [65] from our Reactome analysis are known to be up-regulated in reproductive tissues and other biologic fluids during term labor or PTL with or without infection. CD63 was increased in our study but fetal blood CD63 was not associated with sPTB [66]. "
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    ABSTRACT: Threatened preterm labor (TPTL) is defined as persistent premature uterine contractions between 20 and 37 weeks of gestation and is the most common condition that requires hospitalization during pregnancy. Most of these TPTL women continue their pregnancies to term while only an estimated 5% will deliver a premature baby within ten days. The aim of this work was to study differential whole blood gene expression associated with spontaneous preterm birth (sPTB) within 48 hours of hospital admission. Peripheral blood was collected at point of hospital admission from 154 women with TPTL before any medical treatment. Microarrays were utilized to investigate differential whole blood gene expression between TPTL women who did (n = 48) or did not have a sPTB (n = 106) within 48 hours of admission. Total leukocyte and neutrophil counts were significantly higher (35% and 41% respectively) in women who had sPTB than women who did not deliver within 48 hours (p<0.001). Fetal fibronectin (fFN) test was performed on 62 women. There was no difference in the urine, vaginal and placental microbiology and histopathology reports between the two groups of women. There were 469 significant differentially expressed genes (FDR<0.05); 28 differentially expressed genes were chosen for microarray validation using qRT-PCR and 20 out of 28 genes were successfully validated (p<0.05). An optimal random forest classifier model to predict sPTB was achieved using the top nine differentially expressed genes coupled with peripheral clinical blood data (sensitivity 70.8%, specificity 75.5%). These differentially expressed genes may further elucidate the underlying mechanisms of sPTB and pave the way for future systems biology studies to predict sPTB.
    PLoS ONE 05/2014; 9(5):e96901. DOI:10.1371/journal.pone.0096901 · 3.23 Impact Factor
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    • "CD11b, CD15 and CD66 on granulocytes , and CD11b and CD15 on monocytes in PTB with intact membranes (Gervasi et al. 2001). Similarly, preterm pre-labour rupture of the membranes (PPROM) is associated with upregulation of CD11b, CD14, CD64 and CD66b on granulocytes and CD11b on monocytes (Gervasi et al. 2001). "
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    ABSTRACT: Spontaneous preterm labour and delivery is a syndrome comprising diverse pathological pathways that result in labour and delivery before term. It is recognised that multiple pathological processes are involved, and infection has been well studied and firmly established as a cause. Although the molecular mechanisms responsible for this process have been identified, there is a lack of consensus about effective antibiotic intervention. Systematic reviews of the few well conducted studies suggest that antibiotics active against bacterial vaginosis or related organisms (clindamycin) given to appropriate women (those with objective evidence of abnormal genital tract flora), and used early in pregnancy (< 22 completed weeks of gestation) before irreversible inflammatory damage occurs, can reduce the rate of preterm birth. There is a need for well constructed trials to understand the vaginal microbiome and how the different types of maternal immune response influences outcome.
    Journal of Obstetrics and Gynaecology 11/2013; 33(8):768-75. DOI:10.3109/01443615.2013.842963 · 0.55 Impact Factor
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    • "Gervasi et al. (2001) showed that preterm labour was associated with a significant increase in the expression (as indicated by the median mean channel brightness) of CD11b, CD15 and CD66b on neutrophils and CD11b and CD15 on monocytes. Additionally, an increased ratio of oxidative burst over basal intracellular oxygen radical species production was demonstrated both in neutrophils and in monocytes in preterm labour (Gervasi et al., 2001). Women in labour at term were not studied. "
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    ABSTRACT: We hypothesized that the priming and activation of maternal leukocytes in peripheral blood is a key component of parturition, and that inappropriate preterm priming of leukocytes might initiate preterm labour and delivery. The purpose of this study was to characterize peripheral blood leukocyte activation during human term and preterm labour. We obtained blood samples from pregnant women at term and preterm, both in labour and not in labour. Leukocytes were characterized according to cell subtype and cell surface marker expression. Additionally, we quantified leukocyte cytokine mRNA production, migratory ability and reactive oxygen species production of neutrophils and macrophages. We found that both term and preterm labour were associated with an increase in monocyte and neutrophil proportion or number-neutrophil migratory ability and cell surface marker expression indicating activation. Messenger RNA expression of IL-1beta and IL-8, MCP-1 and TLR-2 was also increased. We conclude that leukocytes in peripheral blood are primed in preparation for activation during term and preterm labour, and that this may contribute to the pathophysiological events of parturition. These data may lead to novel therapies and diagnostic tools for the prevention and/or diagnosis of preterm birth.
    Molecular Human Reproduction 08/2009; 15(11):713-24. DOI:10.1093/molehr/gap054 · 3.75 Impact Factor
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