. A model for hematogenous initiation of placental inflammations
* Department of Pediatrics, University of California, Los Angeles School of Medicine; and
Department of Medical Microbiology and Immunology and the University of Alberta Perinatal Research Centre, Edmonton, Canada
Correspondence: Larry J. Guilbert, Department of Medical Microbiology and Immunology and the University of Alberta Perinatal Research Centre, 6-25 HMRC, University of Alberta, Edmonton, Canada T6G 2S2. E-mail: Larry.Guilbert{at}ualberta.ca
Placental inflammations (villitis) are accompanied by loss of the
syncytiotrophoblast, which is the cellular barrier separating maternal
blood from fetal tissue in the villous placenta. We propose that
syncytiotrophoblast loss is mediated by adhesion of activated maternal
monocytes. This hypothesis was tested with a co-culture model of
peripheral blood monocytes and placental syncytiotrophoblasts. We find
that LPS-activated monocytes adhere to interferon-
(IFN-)-treated
syncytiotrophoblasts via monocyte LFA-1 for >48 h, during which time
the monocytes induce trophoblast apoptosis and subsequent damage of the
trophoblast layer. Optimal monocyte-mediated syncytiotrophoblast death
requires both lipopolysaccharide (LPS) and IFN- and is inhibited by
either anti-tumor necrosis factor (TNF) antibody or epidermal growth
factor. Syncytiotrophoblast damage is largely limited to culture
surfaces in the vicinity of bound monocytes. These results show that
activated maternal monocytes bound to the placental barrier can induce
focal damage mediated by the inflammatory cytokine TNF-
and suggest
a route for maternal leukocyte infiltration into the fetal
stroma.
Key Words: blood • apoptosis • reproductive immunology • adhesion molecules • cytokines
This article has been cited by other articles:
 |
|
 |
|
  J. Madigan, D. J. Freeman, F. Menzies, S. Forrow, S. M. Nelson, A. Young, A. Sharkey, A. Moffett, G. J. Graham, I. A. Greer, et al. Chemokine Scavenger D6 Is Expressed by Trophoblasts and Aids the Survival of Mouse Embryos Transferred into Allogeneic Recipients J. Immunol., March 15, 2010; 184(6): 3202 - 3212. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W Zammiti, N Mtiraoui, H Khairi, J-C Gris, W Y Almawi, and T Mahjoub Associations between tumor necrosis factor-{alpha} and lymphotoxin-{alpha} polymorphisms and idiopathic recurrent miscarriage Reproduction, March 1, 2008; 135(3): 397 - 403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Blois, M. Tometten, J. Kandil, E. Hagen, B. F. Klapp, R. A. Margni, and P. C. Arck Intercellular Adhesion Molecule-1/LFA-1 Cross Talk Is a Proximate Mediator Capable of Disrupting Immune Integration and Tolerance Mechanism at the Feto-Maternal Interface in Murine Pregnancies J. Immunol., February 15, 2005; 174(4): 1820 - 1829. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Berman, G. Girardi, and J. E. Salmon TNF-{alpha} Is a Critical Effector and a Target for Therapy in Antiphospholipid Antibody-Induced Pregnancy Loss J. Immunol., January 1, 2005; 174(1): 485 - 490. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Chan, M.F. Stinski, and L.J. Guilbert Human Cytomegalovirus-Induced Upregulation of Intercellular Cell Adhesion Molecule-1 on Villous Syncytiotrophoblasts Biol Reprod, September 1, 2004; 71(3): 797 - 803. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Chan, D. G. Hemmings, A. D. Yurochko, and L. J. Guilbert Human Cytomegalovirus-Caused Damage to Placental Trophoblasts Mediated by Immediate-Early Gene-Induced Tumor Necrosis Factor-{alpha} Am. J. Pathol., October 1, 2002; 161(4): 1371 - 1381. [Abstract] [Full Text] [PDF]
|
|
