Placental Hofbauer cells and complications of pregnancy
Zhonghua Tang
Department of Obstetrics/Gynecology and Reproductive Sciences, School of Medicine, Yale University, New Haven, Connecticut
Search for more papers by this authorVikki M. Abrahams
Department of Obstetrics/Gynecology and Reproductive Sciences, School of Medicine, Yale University, New Haven, Connecticut
Search for more papers by this authorGil Mor
Department of Obstetrics/Gynecology and Reproductive Sciences, School of Medicine, Yale University, New Haven, Connecticut
Search for more papers by this authorSeth Guller
Department of Obstetrics/Gynecology and Reproductive Sciences, School of Medicine, Yale University, New Haven, Connecticut
Search for more papers by this authorZhonghua Tang
Department of Obstetrics/Gynecology and Reproductive Sciences, School of Medicine, Yale University, New Haven, Connecticut
Search for more papers by this authorVikki M. Abrahams
Department of Obstetrics/Gynecology and Reproductive Sciences, School of Medicine, Yale University, New Haven, Connecticut
Search for more papers by this authorGil Mor
Department of Obstetrics/Gynecology and Reproductive Sciences, School of Medicine, Yale University, New Haven, Connecticut
Search for more papers by this authorSeth Guller
Department of Obstetrics/Gynecology and Reproductive Sciences, School of Medicine, Yale University, New Haven, Connecticut
Search for more papers by this authorAbstract
Hofbauer cells (HBCs) are placental macrophages that are present in the villus across gestation. Despite their identification more than 100 years ago, their specific role in placental function remains largely unelucidated. We initially review aspects of their history and biology as well as evidence for putative sites of origin. To gain insight into their potential function, we then describe complications of pregnancy including villitis of unknown etiology (VUE) and histological chorioamnionitis (HCA), in which alterations in numbers, gene expression, or other characteristics of HBCs have been documented to occur. We further review methods for isolation of HBCs and in vitro studies that explore their role in relation to other major cell types in the placenta and examine their actions in cytokine-mediated inflammation. We conclude that HBCs play a key role in placental pathophysiology, and future advances in their isolation and culture would enable mechanistic insight into their villus function.
References
- 1 Castellucci, M. & P. Kaufmann. 2000. Basic Structure of Villous Trees. In Pathology of the Human Placenta. Springer-Verlag. New York .
10.1007/978-1-4757-4199-5_6 Google Scholar
- 2 Georgiades, P., A.C. Ferguson-Smith & G.J. Burton. 2002. Comparative developmental anatomy of the murine and human definitive placentae. Placenta 23: 3–19.
- 3 Castellucci, M., D. Zaccheo & G. Pescetto. 1980. A three-dimensional study of the normal human placental villous core: I. The Hofbauer cells. Cell Tissue Res. 210: 235–247.
- 4 Fox, H. 1967. The incidence and significance of Hofbauer cells in the mature human placenta. J. Pathol. Bacteriol. 93: 710–717.
- 5 Kim, J.S. et al . 2008. Involvement of Hofbauer cells and maternal T cells in villitis of unknown aetiology. Histopathology. 52: 457–464.
- 6 Kim, M.J. et al . 2009. Villitis of unknown etiology is associated with a distinct pattern of chemokine up-regulation in the feto-maternal and placental compartments: implications for conjoint maternal allograft rejection and maternal anti-fetal graft-versus-host disease. J. Immunol. 182: 3919–3927.
- 7 Wynn, T.A. & L. Barron. 2010. Macrophages: master regulators of inflammation and fibrosis. Semin. Liver Dis. 30: 245–257.
- 8 Seval, Y., E.T. Korgun & R. Demir. 2007. Hofbauer cells in early human placenta: possible implications in vasculogenesis and angiogenesis. Placenta 28: 841–845.
- 9 Khan, S. et al . 2000. Human villous macrophage-conditioned media enhance human trophoblast growth and differentiation in vitro. Biol. Reprod. 62: 1075–1083.
- 10 Anteby, E.Y. et al . 2005. Human placental Hofbauer cells express sprouty proteins: a possible modulating mechanism of villous branching. Placenta 26: 476–483.
- 11 Ingman, K. et al . 2010. Characterisation of Hofbauer cells in first and second trimester placenta: incidence, phenotype, survival in vitro and motility. Placenta 31: 535–544.
- 12 Becroft, D.M., J.M. Thompson & E.A. Mitchell. 2005. Placental villitis of unknown origin: epidemiologic associations. Am. J. Obstet. Gynecol. 192: 264–271.
- 13 Robillard, P.Y. et al . 2007. Etiology of preeclampsia: maternal vascular predisposition and couple disease-mutual exclusion or complementarity? J. Reprod. Immunol. 76: 1–7.
- 14 Myerson, D. et al . 2006. The pathogenesis of villitis of unknown etiology: analysis with a new conjoint immunohistochemistry-in situ hybridization procedure to identify specific maternal and fetal cells. Pediatr. Dev. Pathol. 9: 257–265.
- 15 Redline, R.W. & P. Patterson. 1993. Villitis of unknown etiology is associated with major infiltration of fetal tissue by maternal inflammatory cells. Am. J. Pathol. 143: 473–479.
- 16 Labarrere, C.A., J.A. McIntyre & W.P. Faulk. 1990. Immunohistologic evidence that villitis in human normal term placentas is an immunologic lesion. Am. J. Obstet. Gynecol. 162: 515–522.
- 17 Redline, R.W. 2004. Placental inflammation. Semin. Neonatol. 9: 265–274.
- 18 Hagberg, B. et al . 2001. Changing panorama of cerebral palsy in Sweden. VIII. Prevalence and origin in the birth year period 1991–94. Acta. Paediatr. 90: 271–277.
- 19 Greenwood, C. et al . 2003. Cerebral palsy and clinical negligence litigation: a cohort study. Br. J. Gynaecol. 110: 6–11.
- 20 Redline, R.W. et al . 2005. Placental diagnostic criteria and clinical correlation—a workshop report. Placenta 26(Suppl A): S114–S117.
- 21 Romero, R., T. Chaiworapongsa & J. Espinoza. 2003. Micronutrients and intrauterine infection, preterm birth and the fetal inflammatory response syndrome. J. Nutr. 133: 1668S–1673S.
- 22 Shatrov, J.G. et al . 2010. Chorioamnionitis and cerebral palsy: a meta-analysis. Obstet. Gynecol. 116: 387–392.
- 23 Toti, P. et al . 2010. Focal increase of fetal macrophages in placentas from pregnancies with histological chorioamnionitis (HCA): potential role of fibroblast monocyte chemotactic protein-1 (MCP-1). Am. J.Reprod. Immunology. Advance online publication. doi: 10.1111/j.1600-0897.2010.00927.x.
- 24 Hung, T.H. et al . 2006. Tumour necrosis factor-alpha converting enzyme in human gestational tissues from pregnancies complicated by chorioamnionitis. Placenta 27: 996–1006.
- 25 Vinnars, M.T. et al . 2009. The number of CD68+ (Hofbauer) cells is decreased in placentas with chorioamnionitis and with advancing gestational age. Pediatr. Dev. Pathol. 13: 300–304.
- 26 Abrahams, V.M. et al . 2004. Divergent trophoblast responses to bacterial products mediated by TLRs. J. Immunol. 173: 4286–4296.
- 27 Abrahams, V.M. & G. Mor. 2005. Toll-like receptors and their role in the trophoblast. Placenta 26: 540–547.
- 28 Esplin, M.S. et al . 2005. Monocyte chemotactic protein-1 expression is increased in human gestational tissues during term and preterm labor. Placenta 26: 661–671.
- 29 Kumazaki, K. et al . 2004. Immunohistochemical distribution of Toll-like receptor 4 in term and preterm human placentas from normal and complicated pregnancy including chorioamnionitis. Hum. Pathol. 35: 47–54.
- 30 Satosar, A. et al . 2004. Histologic correlates of viral and bacterial infection of the placenta associated with severe morbidity and mortality in the newborn. Hum. Pathol. 35: 536–545.
- 31 Matsubara, S. et al . 2003. Hofbauer cell activation and its increased glucose-6-phosphate dehydrogenase activity in second trimester-spontaneous abortion: an ultrastructural dual staining enzyme-cytochemical study. Am. J. Reprod. Immunol. 49: 202–209.
- 32 Ojala, T.H. & L.K. Hornberger. 2010. Fetal heart failure. Front. Biosci. (Schol. Ed.) 2: 891–906.
- 33 Delbecque, K., S. Gaillez & J.P. Schaaps. 2009. Histopathological diagnosis of a type vii mucopolysaccharidosis after pregnancy termination. Fetal Pediatr. Pathol. 28: 1–8.
- 34 Nelson, J. et al . 1993. Foamy changes of placental cells in probable beta glucuronidase deficiency associated with hydrops fetalis. J. Clin. Pathol. 46: 370–371.
- 35 Pilz, I., G. Schweikhart & P. Kaufmann. 1980. Problems of distinction of normal, arteficial and pathological structures in mature human placental villi: III. Morphometric studies in rhesus incompatibility (author's transl.). Arch. Gynecol. 229: 137–154.
- 36 Roberts, D.J., M.G. Ampola & J.M. Lage. 1991. Diagnosis of unsuspected fetal metabolic storage disease by routine placental examination. Pediatr. Pathol. 11: 647–656.
- 37 Hunt, J.S., C.R. King, Jr. & G.W. Wood. 1984. Evaluation of human chorionic trophoblast cells and placental macrophages as stimulators of maternal lymphocyte proliferation in vitro. J. Reprod. Immunol. 6: 377–391.
- 38 Uren, S. & W. Boyle. 1985. Isolation of macrophages from human placenta. J. Immunol. Methods 78: 25–34.
- 39 Wilson, C.B., J.E. Haas & W.M. Weaver. 1983. Isolation, purification and characteristics of mononuclear phagocytes from human placentas. J. Immunol. Methods 56: 305–317.
- 40 Pavlov, O.V. et al . 1998. Production of cultured human placental macrophages. Biull. Eksp. Biol. Med. 125: 579–582.
- 41 Sutton, L.N., D.Y. Mason & C.W. Redman. 1989. Isolation and characterization of human fetal macrophages from placenta. Clin. Exp. Immunol. 78: 437–443.
- 42 Zaccheo, D. et al . 1989. Isolation and characterization of Hofbauer cells from human placental villi. Arch. Gynecol. Obstet. 246: 189–200.
- 43 McIntire, R.H. et al . 2006. In vitro models for studying human uterine and placental macrophages. Methods Mol. Med. 122: 123–148.
- 44 Wetzka, B. et al . 1997. Isolation of macrophages (Hofbauer cells) from human term placenta and their prostaglandin E2 and thromboxane production. Hum. Reprod. 12: 847–852.
- 45 Douglas, G.C. & B.F. King. 1989. Isolation of pure villous cytotrophoblast from term human placenta using immunomagnetic microspheres. J. Immunol. Methods. 119: 259–268.
- 46 Guller, S. et al . 2008. Placental expression of ceruloplasmin in pregnancies complicated by severe preeclampsia. Lab. Invest. 88: 1057–1067.
- 47 Guller, S. et al . 1993. Glucocorticoid suppression of human placental fibronectin expression: implications in uterine-placental adherence. Endocrinology 133: 1139–1146.
- 48 Kliman, H.J. et al . 1986. Purification, characterization, and in vitro differentiation of cytotrophoblasts from human term placentae. Endocrinology 118: 1567–1582.
- 49 Petroff, M.G. et al . 2006. Isolation and culture of term human trophoblast cells. Methods Mol. Med. 121: 203–217.
- 50 Bonet, B. et al . 1992. Metabolism of very-low-density lipoprotein triglyceride by human placental cells: the role of lipoprotein lipase. Metabolism 41: 596–603.
- 51 Cervar, M. et al . 1999. Paracrine regulation of distinct trophoblast functions in vitro by placental macrophages. Cell Tissue Res. 295: 297–305.
- 52 Nagamatsu, T. & D.J. Schust. 2010. The immunomodulatory roles of macrophages at the maternal-fetal interface. Reprod. Sci. 17: 209–218.
- 53 Redman, C.W. & I.L. Sargent. 2005. Latest advances in understanding preeclampsia. Science 308: 1592–1594.
- 54 Sharma, S., W.E. Norris & S. Kalkunte. 2010. Beyond the threshold: an etiological bridge between hypoxia and immunity in preeclampsia. J. Reprod. Immunol. 85: 112–116.