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Specific sensitivity of CD43 to neutrophil elastase [see comments]
E Remold-O'Donnell and D Parent
Center for Blood Research, Harvard Medical School, Boston, MA.
CD43 (sialophorin, leukosialin), an O-glycosylated and sialylated membrane
protein (surface sialomucin) with antiadhesive properties, is thought to
protect circulating leukocytes by preventing cell surface interactions.
Although it is resistant to several proteases, the granule enzyme elastase
was recently implicated in loss of extracellular CD43 regions from
incubated neutrophils. Flow cytometry showed that neutrophil CD43 is
cleaved by low levels of neutrophil elastase with half-maximal cleavage at
5 micrograms/mL; pancreatic elastase, in contrast, did not cleave CD43.
Related neutrophil granule proteases proteinase-3 and cathepsin-G did not
cleave CD43 or required greater than 10-fold higher enzyme levels,
respectively. The 115-kD CD43 isoform on T-lymphoid cells, which differs in
glycosylation from 135-kD neutrophil CD43, was equally sensitive to
neutrophil elastase, suggesting that cleavage susceptibility extends to
various leukocytes. Enzymatic removal of sialic acid did not facilitate
CD43 cleavage by neutrophil elastase, a feature that distinguishes the
action of neutrophil elastase from other proteases. Western blots of
elastase- treated neutrophils detected an 83-kD CD43 fragment that,
together with the released 52-kD fragment and 40-kD subfragment, accounts
for the entire molecule and indicates that CD43 is cleaved at two sites
only, releasing the distal approximately 40% of the sialomucin region. The
specificity of the CD43 cleaving reaction was shown by the insensitivity of
other neutrophil and lymphoid surface proteins to elastase levels that
deplete CD43. Exceptions were P-selectin glycoprotein ligand-1 on
neutrophils, also a surface mucin, and CD16 (Fc gamma RIII), which was
previously characterized as elastase sensitive. The sensitivity and
specificity of CD43 cleavage by neutrophil elastase, the very high levels
of elastase in human neutrophils and its ready release by stimulating
conditions suggest important physiologic/pathologic roles for this CD43
cleaving reaction.
Volume 86,
Issue 6,
pp. 2395-2402,
09/15/1995
Copyright © 1995 by The American Society of Hematology

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