Spermicidal Activity of Bacterial Lipopolysaccharide Is Only Partly Due to Lipid A

Authors

  • Hamid Hakimi,

    1. Division of Genomic Medicine, The Medical School, The University of Sheffield, Sheffield, United Kingdom.
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  • Ian Geary,

    1. Division of Genomic Medicine, The Medical School, The University of Sheffield, Sheffield, United Kingdom.
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  • Allan Pacey,

    1. Division of Clinical Sciences, The Jessop Wing, Central Sheffield University Hospitals Trust, The University of Sheffield, Sheffield, United Kingdom.
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  • Adrian Eley

    Corresponding author
    1. Division of Genomic Medicine, The Medical School, The University of Sheffield, Sheffield, United Kingdom.
      Dr Adrian Eley, Division of Genomic Medicine, The Medical School, The University of Sheffield, Sheffield, S10 2RX, United Kingdom (e-mail: a.r.eley@sheffield.ac.uk).
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Dr Adrian Eley, Division of Genomic Medicine, The Medical School, The University of Sheffield, Sheffield, S10 2RX, United Kingdom (e-mail: a.r.eley@sheffield.ac.uk).

Abstract

ABSTRACT: We have previously shown that co-incubation of Chlamydia trachomatis lipopolysaccharide (LPS) leads to premature sperm death by an apoptosis-like mechanism. It was always assumed that lipid A is the toxic component of LPS. Here we investigate the possible involvement of 3-deoxy-d-manno-octulosonic acid (Kdo), which is an additional component of the LPS in C. trachomatis. Highly motile preparations of sperm from normozoospermic patients were incubated for 6 hours with commercial sources of lipid A and Kdo. Conventional lipid A inhibitors, polymyxin B (PMB) and anti-CD14 monoclonal antibody (mAb) were used to test the ability of both lipid A and Kdo to induce an apoptotic-like response in mature sperm. Flow cytometry was used to determine apoptosis by the expression of annexin V. Caspase activity was also measured by fluorometry and by the use of a pan-caspase inhibitor and caspase-3 inhibitor. Both lipid A and Kdo at 50 μg/mL caused significant mortality of sperm. However, although PMB and anti-CD14 mAb were inhibitory to the activity of lipid A on sperm, no such effect was seen against Kdo. In the presence of either lipid A or Kdo, sperm death was caused by an apoptotic-like effect that was caspase mediated. We conclude that Kdo shares its spermicidal properties with lipid A and seems to kill sperm in a similar manner. These results provide an explanation for higher than expected levels of spermicidal activity of LPS that are not caused by lipid A.

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