Abstract
CD14 is a 56 Kd glycoprotein typically present on myeloid cells and originally implicated in innate immunity and pattern recognition. The possible involvement of its membrane bound form with the clearance of apoptotic cells and its recently demonstrated expression by non-myeloid cells, make this fascinating molecule a target for more research and possible therapeutic use. The objective of this study was to assess the possible anti apoptotic effect of the soluble form of CD14, on human lymphocytes and to delineate the fragment, from within the protein that may be mediating that activity. Human peripheral blood lymphocytes were cultured in vitro and induced for apoptosis with gliotoxin, with or without the addition of rhCD14 or CD14 peptide. As controls, we used lymphocyte cell lines such as Jurkat, NK-YTS and also normal peripheral blood neutrophils. We demonstrate that human soluble CD14 is capable of protecting human lymphocytes from gliotoxin- induced apoptosis in vitro. It is not capable of protecting gliotoxin-treated apoptotic Jurkat or NK-YTS cells. Moreover, we reveal that a fragment of the protein, a peptide that is recognized by the MO2 monoclonal anti-CD14 antibody, retains this protective effect, although with a lower efficiency. We have previously shown that the MO2 epitope was found naturally inside human lymphocytes. Here, we demonstrate that the MO2 peptide can penetrate lymphocytes in human peripheral blood mononuclear cells incubated in vitro. The peptide does not penetrate Jurkat or NK-YTS cells and it does not protect them from apoptosis. In addition, peripheral blood neutrophils, in which the peptide penetration was much better than in lymphocytes, could not be protected by this peptide from their spontaneous apoptosis in vitro.Our data thus suggest that circulating CD14 may play an important role in the prevention of apoptosis of lymphocytes and that a specific region from within the molecule is involved in this activity.
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Tartakovsky, B., Sredni, B., Zigman-Hoffman, E. et al. A Peptide of CD14 Protects Human Lymphocytes from Gliotoxin-Induced Apoptosis. Int J Pept Res Ther 18, 249–258 (2012). https://doi.org/10.1007/s10989-012-9298-8
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DOI: https://doi.org/10.1007/s10989-012-9298-8