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CD14 And A Peptide Thereof For Protection Of Cells Against
Apoptosis
Boris Tartakovsky, PhD and Ella Naparstek, MD
Background
CD14 is a 55-kDa protein present on the surface membrane of
phagocytic leukocytes and possibly of other cells. It is also present in a
soluble form in serum. CD14 is one of the major molecules responsible for the
innate host immune response to microbial infection. We have been very much
interested by the interaction of soluble CD14 with human lymphocytes and
have recently identified a subpopulation of human lymphocytes expressing an
intracellular CD14 epitope.
Summary of the invention
The present discovery is based on our surprising and original finding
that soluble CD14 protects human lymphocytes from death, specifically from
apoptotic cell death. Moreover, a fragment from within the CD14 molecule
that mediates the protection from apoptosis, a peptide of 22 amino acids, has
been characterized and synthesized. This peptide was found to retain the
anti-apoptotic activity of the complete CD14 protein.
Applications
Examples of pathological or clinical situations in which blocking
apoptosis is essential include, among others, hematopoietic stem cell
transplantation, immune deficiencies, infectious diseases (including for
example, HIV), autoimmune diseases, central nervous system disorders, heart
diseases, and aging.
Conclusions
We have discovered a novel function of the soluble CD14, namely
protecting lymphocytes from apoptosis. We have identified, synthesized, and
employed the active anti-apoptotic peptide of the molecule. We seek to
develop an anti-apoptotic drug based on its amino acid sequence. A patent
application, protecting the constitution and use of the peptide, has been filed.
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