Format

Send to:

Choose Destination
See comment in PubMed Commons below
Am J Reprod Immunol. 2009 Aug;62(2):96-111. doi: 10.1111/j.1600-0897.2009.00717.x.

Antiphospholipid antibodies induce a pro-inflammatory response in first trimester trophoblast via the TLR4/MyD88 pathway.

Author information

  • 1Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06510, USA.

Abstract

PROBLEM:

Women with antiphospholipid antibodies (aPL) are at risk for recurrent miscarriage, pre-eclampsia, and pre-term labor. aPL target the placenta directly by binding to beta(2)-glycoprotein I (beta(2)GPI) expressed on the surface of trophoblast cells. The objective of this study was to determine the effects of aPL on trophoblast function and the mechanisms involved.

METHOD OF STUDY:

First trimester trophoblast cells were treated with anti-beta(2)GPI monoclonal antibodies and patient-derived aPL, after which cell survival and function was evaluated.

RESULTS:

We report that anti-beta(2)GPI antibodies trigger an inflammatory response in trophoblast, characterized by increased secretion of interleukin (IL)-8, MCP-1, GRO-alpha, and IL-1beta, and that this occurs in a TLR-4/MyD88-dependent manner. At high concentrations, these antibodies also induce caspase-mediated cell death. This was attenuated upon disabling of the MyD88 pathway, suggesting that anti-beta(2)GPI-induced inflammatory mediators compromise trophoblast survival by acting in an autocrine/paracrine manner. Enhanced IL-8, GRO-alpha, and IL-1beta secretion also occurred when trophoblast cells were incubated with antibodies from patients with antiphospholipid syndrome. Heparin, which acts as a pro-survival factor in human trophoblast, attenuated the anti-beta(2)GPI antibody-mediated cell death, and also the pro-inflammatory response, but only at high concentrations.

CONCLUSION:

These findings demonstrate that aPL triggers a placental inflammatory response via the TLR-4/MyD88 pathway, which in turn compromises trophoblast survival. Thus, the TLR-4/MyD88 pathway may provide a new therapeutic target to improve pregnancy outcome in antiphospholipid syndrome patients.

PMID:
19614626
[PubMed - indexed for MEDLINE]
PMCID:
PMC2772057
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Blackwell Publishing Icon for PubMed Central
    Loading ...
    Write to the Help Desk