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Abstract:

study hypothesis: Is apoptotic cell phagocytosis by monocytes modulated by pathways elicited by vasoactive intestinal peptide (VIP) action on trophoblast? study finding: Targeting trophoblast cells with VIP induces monocyte migration, polarization to anti-inflammatory phenotypes and apoptotic trophoblast cell clearance which involves increased αvβ3 integrin expression on phagocytic cells and binding to thrombospondin 1. what is known already: Monocytes recruited to the maternal-placental interface interact with trophoblast cells and differentiate to alternatively activated macrophages involved in the silent clearance of apoptotic cells. Vasoactive intestinal peptide (VIP) is an immunomodulatory polypeptide synthesized at the human placenta that can target both trophoblast cells and monocytes/macrophages. Integrin αvβ3 and thrombospondin 1 are involved in the formation of a phagocytic portal for the immunosuppressant clearance of apoptotic cells. study design, samples/materials, methods: This is a laboratory-based study studying monocytes isolated from peripheral blood of healthy women (n = 33) and their interaction in vitro with first trimester trophoblast cell lines. Peripheral blood monocytes were isolated from healthy volunteers by Percoll gradient and tested in co-culture settings with first trimester trophoblast cell lines (Swan 71 and HTR8) or with trophoblast cell conditioned media obtained in the presence or absence of 10 or 100 nM VIP. The effect of VIP-conditioned media on monocyte migration was assessed through transwell systems and monocyte/macrophage phenotype was determined by flow cytometry. Phagocytosis of apoptotic cells and the mechanisms involved in phagocytic portal formation were assessed byflowcytometry, confocal microscopy, immunological blockade and RT-PCR. mainresults andthe role of chance: Exposing cells to 100 nM VIP increased the migration of monocytes toward trophoblast cell conditioned media (VIP conditioned medium) (P < 0.05 versus conditioned media from cells not exposed to VIP) and contributed to the monocytes acquiring an anti-inflammatory profile with increased CD39 and IL-10 expression (P < 0.05). Phagocytosis of apoptotic trophoblast cells by monocytes and monocyte-differentiated macrophages was increased by VIP conditioned medium (P < 0.05 versus media conditioned in the absence of VIP or direct addition of 100 nM VIP). The boosting effect of VIP conditioned medium on phagocytosis involved increased expression and re-localization of αvβ3 integrin on phagocytic cells along with enhanced expression of thrombospondin 1 on trophoblast cells. limitations, reasons for caution: The conclusions are based on in vitro experiments with monocytes drawn from peripheral blood of healthy individuals and trophoblast cell lines and we were unable to ascertain that these mechanisms operate similarly in vivo.We cannot rule out a differential behavior of either trophoblast cells targeted in vivo with VIP, or primary cultures of first trimester trophoblast cells assayed in vitro. wider implications of the findings: The results presented provide new clues for immune and trophoblast cell pharmacological targeting in pregnancy complications of immunopathologic nature. study funding/competing interest(s): This work was funded by the National Agency of Sciences and Technology ANPCyT (PICT 2011-0144), National Research Council CONICET (PIP 602/2012) and University of Buenos Aires (UBACyT 20020130100040BA) to C.P.L. The authors have no conflicts of interest to disclose. © The Author 2015.

Registro:

Documento: Artículo
Título:Trophoblast cells primed with vasoactive intestinal peptide enhance monocyte migration and apoptotic cell clearance through αvβ3 integrin portal formation in a model of maternal-placental interaction
Autor:Grasso, E.; Calo, G.; Vota, D.; Hauk, V.; Ramhorst, R.; Leirós, C.P.
Filiación:Department of Biological Chemistry, School of Sciences, University of Buenos Aires, IQUIBICEN-CONICET, Ciudad Universitaria, Pab. 2, Buenos Aires, 1428, Argentina
Palabras clave:Apoptotic cell phagocytosis; Apoptotic trophoblast cells; Maternal-placental interface; Monocytes; Thrombospondin I; Vasoactive intestinal polypeptide; CD39 antigen; interleukin 10; thrombospondin 1; vasoactive intestinal polypeptide; vitronectin receptor; vasoactive intestinal polypeptide; vitronectin receptor; Article; cell clearance; cell differentiation; cell line; cell migration; cell phagocytosis; cellular parameters; coculture; controlled study; female; filters and membranes; first trimester pregnancy; flow cytometry; homeostasis; HTR8 cell line; human; human cell; in vitro study; macrophage activation; maternal placental interface; monocyte; normal human; parameters concerning the fetus, newborn and pregnancy; priority journal; protein expression; protein localization; reverse transcription polymerase chain reaction; Swan 71 cell line; trophoblast; upregulation; apoptosis; drug effects; metabolism; monocyte; placenta; pregnancy; trophoblast; Apoptosis; Female; Humans; Integrin alphaVbeta3; Monocytes; Placenta; Pregnancy; Trophoblasts; Vasoactive Intestinal Peptide
Año:2015
Volumen:21
Número:12
Página de inicio:930
Página de fin:941
DOI: http://dx.doi.org/10.1093/molehr/gav059
Título revista:Molecular Human Reproduction
Título revista abreviado:Mol. Hum. Reprod.
ISSN:13609947
CODEN:MHREF
CAS:CD39 antigen, 161818-29-7; thrombospondin 1, 343987-56-4; vasoactive intestinal polypeptide, 37221-79-7; Integrin alphaVbeta3; Vasoactive Intestinal Peptide
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13609947_v21_n12_p930_Grasso

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Citas:

---------- APA ----------
Grasso, E., Calo, G., Vota, D., Hauk, V., Ramhorst, R. & Leirós, C.P. (2015) . Trophoblast cells primed with vasoactive intestinal peptide enhance monocyte migration and apoptotic cell clearance through αvβ3 integrin portal formation in a model of maternal-placental interaction. Molecular Human Reproduction, 21(12), 930-941.
http://dx.doi.org/10.1093/molehr/gav059
---------- CHICAGO ----------
Grasso, E., Calo, G., Vota, D., Hauk, V., Ramhorst, R., Leirós, C.P. "Trophoblast cells primed with vasoactive intestinal peptide enhance monocyte migration and apoptotic cell clearance through αvβ3 integrin portal formation in a model of maternal-placental interaction" . Molecular Human Reproduction 21, no. 12 (2015) : 930-941.
http://dx.doi.org/10.1093/molehr/gav059
---------- MLA ----------
Grasso, E., Calo, G., Vota, D., Hauk, V., Ramhorst, R., Leirós, C.P. "Trophoblast cells primed with vasoactive intestinal peptide enhance monocyte migration and apoptotic cell clearance through αvβ3 integrin portal formation in a model of maternal-placental interaction" . Molecular Human Reproduction, vol. 21, no. 12, 2015, pp. 930-941.
http://dx.doi.org/10.1093/molehr/gav059
---------- VANCOUVER ----------
Grasso, E., Calo, G., Vota, D., Hauk, V., Ramhorst, R., Leirós, C.P. Trophoblast cells primed with vasoactive intestinal peptide enhance monocyte migration and apoptotic cell clearance through αvβ3 integrin portal formation in a model of maternal-placental interaction. Mol. Hum. Reprod. 2015;21(12):930-941.
http://dx.doi.org/10.1093/molehr/gav059