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Metalloprotease activity of CD13/aminopeptidase N on the surface of human
myeloid cells
RA Ashmun and AT Look
Department of Hematology/Oncology, St Jude Children's Research Hospital,
Memphis, TN 38101.
We previously found that the myeloid cell surface glycoprotein CD13 (gp150)
is identical to aminopeptidase N (EC 3.4.11.2), a widely distributed
membrane-bound, zinc-dependent metalloprotease with an extracellular
enzymatic domain that cleaves N-terminal amino acid residues from
oligopeptides (J Clin Invest 83:1299, 1989). As a first step toward
defining the function of this molecule on myeloid cells, we assessed cell
surface-associated N-terminal peptidase activity by sensitive
spectrophotometric measurements of the cleavage of p- nitroanilide amino
acid derivatives. Aminopeptidase activity detected on the surface of normal
and malignant hematopoietic cells coincided with the level of cell surface
CD13 expression as measured by flow cytometry. The enzyme was specifically
inhibited by the zinc-binding metalloprotease inhibitors, bestatin,
1,10-phenanthroline, or 2.2'- dipyridyl, but was not affected by several
inhibitors of other classes of proteases. Aminopeptidase activity was
demonstrated for CD13 molecules specifically immunoprecipitated from the
surface of CD13- positive cells and was blocked by the metalloprotease
inhibitor 1,10- phenanthroline. Moreover, cell surface aminopeptidase
activity was partially inhibited when viable cells were incubated with two
of a panel of 11 monoclonal antibodies (MoAbs) known to be specific for
extracellular epitopes of human CD13. This inhibition was apparent in the
absence of detectable downmodulation of CD13 molecules from the cell
surface, suggesting that these MoAbs either physically interfere with
substrate binding or alter the zinc-coordinating properties of
aminopeptidase N molecules. Aminopeptidase N could play an important role
in modulating signals generated by peptides at the surface of myeloid
cells, either by removing key N-terminal residues from active peptides or
by converting inactive peptides to active forms. The inhibitory antibodies
used in this study should prove useful in delineating the physiologic roles
of CD13/aminopeptidase N on normal and malignant myeloid cells.
Volume 75,
Issue 2,
pp. 462-469,
01/15/1990
Copyright © 1990 by The American Society of Hematology
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