Chemokines and Leukocyte Activation in the Fetal Circulation During Preeclampsia

Mellembakken, Jan Roar; Aukrust, Pål; Hestdal, Kjetil; Ueland, Thor; Åbyholm, Thomas; Videm, Vibeke

doi:10.1161/01.hyp.38.3.394

Cited by 61 publications

(50 citation statements)

References 25 publications

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“…Consequently, we propose the hypothesis that leakage of fluids and proteins could result in edema and proteinuria, conditions observed in women with preeclampsia. 41,42 The maternal vascular system undergoes an inflammatory process during preeclampsia, as evidenced by increased neutrophil activation [43][44][45][46] and vascular neutrophil infiltration. 6 -8 In the early phase of this study, we hypothesized that infiltrating neutrophils could affect expression of genes related to the extracellular matrix.…”

Section: Discussionmentioning

confidence: 99%

Increased Expression of Matrix Metalloproteinase-1 in Systemic Vessels of Preeclamptic Women

Estrada-Gutiérrez

Cappello

Mishra

et al. 2011

The American Journal of Pathology

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This study was conducted to determine the following: (1) whether matrix metalloproteinase-1 (MMP-1) is increased in systemic vessels of preeclamptic women, (2) whether this increase might be mediated by neutrophils, and (3) whether MMP-1 could be responsible for vascular dysfunction. Omental arteries and plasma were collected from healthy pregnant and preeclamptic women. Omental arteries were evaluated for gene and protein expression of MMP-1, collagen type 1␣, tissue inhibitor of metalloproteinase-1, and vascular reactivity to MMP-1. Gene and protein expression levels were also evaluated in human vascular smooth muscle cells (VSMCs) co-cultured with activated neutrophils, reactive oxygen species, or tumor necrosis factor ␣. Vessel expression of MMP-1 and circulating MMP-1 levels were increased in preeclamptic women, whereas vascular expression of collagen or tissue inhibitor of metalloproteinase-1 were down-regulated or unchanged. In cultured VSMCs, the imbalance in collagen-regulating genes of preeclamptic vessels was reproduced by treatment with neutrophils, tumor necrosis factor ␣, or reactive oxygen species. Chemotaxis studies with cultured cells revealed that MMP-1 promoted recruitment of neutrophils via vascular smooth muscle release of interleukin-8. Furthermore, MMP-1 induced vasoconstriction via protease-activated receptor-1, whose expression was significantly increased in omental arteries of preeclamptic women and in VSMCs co-cultured with neutrophils. Collectively, these findings disclose a novel role for MMP-1 as a mediator of vasoconstriction and vascular dysfunction in preeclampsia.

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Section: Discussionmentioning

confidence: 99%

Increased Expression of Matrix Metalloproteinase-1 in Systemic Vessels of Preeclamptic Women

Estrada-Gutiérrez

Cappello

Mishra

et al. 2011

The American Journal of Pathology

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“…Among the chemokines studied, the mean serum EOX concentration was found to be 80 pg/mL and was higher than our result (median, 36 pg/mL). One possible explanation is that we have excluded neonates who were born to mothers with stressful medical diseases such as preeclampsia, which might induce the activation of leukocytes and chemokine cascades in the fetal circulation (19). Our study also excluded neonates with clinical sepsis, which could also increase serum chemokine levels (20 -22).…”

Section: Discussionmentioning

confidence: 99%

Helper T-Lymphocyte–Related Chemokines in Healthy Newborns

Leung

Tam

et al. 2004

Pediatr Res

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Atopic disease is characterized by an imbalance in cytokines secreted from Th1 and Th2 lymphocytes. The association between atopy and serum levels of atopy-related chemokines in umbilical cord blood (UCB) has not been evaluated. This study formulates the reference ranges of thymus and activationregulated chemokine (TARC), macrophage-derived chemokine (MDC), eotaxin (EOX), monocyte chemotactic protein 1 (MCP-1), and interferon-␥-inducible protein 10 (IP-10) in UCB of term neonates and investigates the relation between these chemokines and the development of atopy during infancy. The concentrations of total IgE and chemokines in UCB serum were measured by microparticle immunoassay and sandwich enzyme immunoassay, respectively. A total of 124 singleton healthy newborns were investigated. Fifty-three (43%) infants had family history of allergic diseases, and 26 (21%) had increased serum total IgE concentrations. The median (interquartile range) serum TARC, MDC, EOX, MCP-1, and IP-10 concentrations, in pg/mL, were 425 (300 -639), 786 (561-1050), 36 (28 -45), 156 (116 -205), and 38 (29 -49), respectively. Multiparity was associated with increased serum MDC (p ϭ 0.017). Serum chemokine concentrations were not associated with total IgE levels or family history of allergies. The median (interquartile range) serum MDC concentrations in newborns who developed wheezing during infancy and those without wheezing were 1259 pg/mL (945-1523) and 782 pg/mL (551-992), respectively (p ϭ 0.010). This study provides reference ranges of Th-specific chemokines in UCB serum of singleton term neonates. Increased serum MDC concentrations at birth are associated with the occurrence of wheezing during infancy. Asthma and atopy are characterized by an overproduction of type-2 helper T (Th2) lymphocyte-related cytokines such as IL-4, IL-5, and IL-13 and a relative deficiency of Th1-related interferon-␥ (IFN-␥), IL-2, and IL-12 (1). Chemokines are a family of cytokines involved in the trafficking of leukocytes to the site of inflammation (2). Chemokines have been classified into four groups-C, C-C, C-X-C and C-X 3 -C-depending on the number and spacing of conserved cysteines. Recently, it was suggested that the expression of some chemokines could be preferentially associated with a Th1 or a Th2 immune response. The differential expression of chemokine receptors may dictate the actions of chemokines and their involvement in mechanisms of polarized Th1-and Th2-mediated immune responses (3, 4). The expression of CC chemokines, such as eotaxin (EOX) (5, 6), thymus and activation-regulated chemokine (TARC) (7, 8), macrophage-derived chemokine (MDC) (9, 10), and monocyte chemotactic protein 1 (MCP-1) (11, 12), has been studied mainly in Th2-mediated allergic diseases. These molecules are chemotactic for eosinophils, lymphocytes, and monocytes (2, 13). In contrast, the C-X-C chemokine IFN-␥-inducible protein 10 (IP-10) is chemotactic for neutrophils and lymphocytes (14). The expression of IP-10 is upregulated in many Th1-type inflammatory diseases (6...

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“…8 In addition, mouse monoclonal antibodies to human CD35 (complement receptor, CR 1), CD55 (decay accelerating factor, DAF), and CD59 (complement protectin) were purchased from Pharmingen, and CD46 (membrane cofactor protein, MCP) and CD88 (C5a receptor) from Serotec.…”

Section: Staining and Flow Cytometry Analysismentioning

confidence: 99%

Activation of Leukocytes During the Uteroplacental Passage in Preeclampsia

Mellembakken¹,

Aukrust²,

Olafsen³

et al. 2002

Hypertension

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152

105

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Abstract-Endothelial dysfunction and inflammation appear to play a major role in the pathogenesis of preeclampsia. We hypothesize that a chronic inflammation in the decidua and placenta during preeclampsia may lead to a local leukocyte activation in this compartment. Venous blood was sampled simultaneously from antecubital and uterine veins during cesarean sections in 30 women with preeclampsia, 29 with uncomplicated pregnancies, and from 17 nonpregnant women. The expression of adhesion molecules and complement-related markers on neutrophils and monocytes was analyzed by flow cytometry. In patients with preeclampsia, neutrophil expression of the integrins CD11a, CD11b, and CD11c and of the complement related markers CD35 and CD59 was significantly higher in samples from uterine than from antecubital veins. No differences were found in nonpregnant women. On monocytes the expression of the Sialyl Lewis x antigen, the integrins CD11a, CD11c, and CD49d, and the complement-related markers CD46 and CD59 was higher in samples from uterine than from antecubital veins during preeclampsia, but not in uncomplicated pregnancies, whereas in nonpregnant women CD31 was decreased. Our findings suggest activation of neutrophils and monocytes taking place during the uteroplacental passage in preeclamptic, but not in normal pregnancies. Such a local inflammatory response involving enhanced leukocyte/endothelial interaction may contribute to the pathogenesis of this disorder.

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Chemokines and Leukocyte Activation in the Fetal Circulation During Preeclampsia

Cited by 61 publications

References 25 publications

Increased Expression of Matrix Metalloproteinase-1 in Systemic Vessels of Preeclamptic Women

Increased Expression of Matrix Metalloproteinase-1 in Systemic Vessels of Preeclamptic Women

Helper T-Lymphocyte–Related Chemokines in Healthy Newborns

Activation of Leukocytes During the Uteroplacental Passage in Preeclampsia

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