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Activated Macrophages Inhibit Human Cytotrophoblast Invasiveness In Vitro

RENAUD, Stephen J ; POSTOVIT, Lynne-Marie ; MACDONALD-GOODFELLOW, Shannyn K ; MCDONALD, Gail T ; CALDWELL, Jason D ; GRAHAM, Charles H

Biology of reproduction, 2005-08, Vol.73 (2), p.237-243 [Periódico revisado por pares]

Madison, WI: Society for the Study of Reproduction

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Título:
Activated Macrophages Inhibit Human Cytotrophoblast Invasiveness In Vitro
Autor: RENAUD, Stephen J ; POSTOVIT, Lynne-Marie ; MACDONALD-GOODFELLOW, Shannyn K ; MCDONALD, Gail T ; CALDWELL, Jason D ; GRAHAM, Charles H
Assuntos: Apoptosis - immunology ; Biological and medical sciences ; Cell Movement - immunology ; Coculture Techniques ; Embryology: invertebrates and vertebrates. Teratology ; Enzyme-Linked Immunosorbent Assay ; Extracellular Matrix - immunology ; Female ; Fetal membranes ; Fundamental and applied biological sciences. Psychology ; General aspects. Development. Fetal membranes ; Humans ; Lipopolysaccharides - pharmacology ; Macrophage Activation - immunology ; Macrophages - cytology ; Macrophages - drug effects ; Macrophages - immunology ; Male ; Plasminogen Activator Inhibitor 1 - secretion ; Pregnancy ; Trophoblasts - cytology ; Trophoblasts - enzymology ; Trophoblasts - immunology ; Trophoblasts - secretion ; Tumor Necrosis Factor-alpha - immunology ; Urokinase-Type Plasminogen Activator - secretion ; Vertebrates: reproduction
É parte de: Biology of reproduction, 2005-08, Vol.73 (2), p.237-243
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Descrição: Pre-eclampsia is associated with inadequate cytotrophoblast invasion and remodeling of the uterine spiral arterioles, as well as by an aberrant maternal immune response. This study determined the effect of activated macrophages and one of its products, tumor necrosis factor (TNF)-alpha, on cytotrophoblast invasiveness. Coculture with human lipopolysaccharide-activated macrophages decreased the ability of immortalized HTR-8/ SVneo human trophoblast cells to invade through reconstituted extracellular matrix ( P < 0.05). This effect of activated macrophages on trophoblast invasiveness was paralleled by abrogation of a 55-kDa caseinolytic activity corresponding to prourokinase plasminogen activator (pro-uPA) and an increased secretion of plasminogen activator inhibitor 1 (PAI1), as determined by gel zymography and ELISA, respectively. Coculture with nonactivated macrophages did not significantly affect trophoblast invasiveness or pro-uPA and PAI1 secretion. Activated macrophages secreted detectable levels of TNF, and administration of exogenous TNF significantly decreased trophoblast invasiveness ( P < 0.05), increased the secretion of PAI1 ( P < 0.01), and completely inhibited the pro-uPA-associated caseinolytic activity by binding to the TNF receptor 1. Moreover, addition of up to 10 ng/ml of TNF did not increase the rate of apoptosis in HTR-8/SVneo cells. Finally, the increased secretion of PAI1 by trophoblast cells cocultured with activated macrophages was significantly inhibited when a neutralizing anti-TNF antibody was added to the cocultures. These results suggest that the aberrant presence of activated macrophages around uterine vessels may contribute to inadequate trophoblast invasion and remodeling of the uterine spiral arterioles. Thus, the presence of activated macrophages may be important in the etiology of pre-eclampsia. Abstract Macrophage-mediated inhibition of trophoblast invasion may be critical to the etiology of pre-eclampsia
Editor: Madison, WI: Society for the Study of Reproduction
Idioma: Inglês

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Activated Macrophages Inhibit Human Cytotrophoblast Invasiveness In Vitro

RENAUD, Stephen J ; POSTOVIT, Lynne-Marie ; MACDONALD-GOODFELLOW, Shannyn K ; MCDONALD, Gail T ; CALDWELL, Jason D ; GRAHAM, Charles H

Madison, WI: Society for the Study of Reproduction

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