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Effects of human neutrophil elastase (HNE) on neutrophil function in vitro
and in inflamed microvessels
RC Woodman, PH Reinhardt, S Kanwar, FL Johnston and P Kubes
Department of Medical Physiology and Medicine, University of Calgary,
Alberta, Canada.
The primary objective of this study was to test the hypothesis that human
neutrophil elastase (HNE) affects neutrophil infiltration (adhesion and
emigration) into inflamed vessels. To determine whether HNE contributes to
neutrophil adhesion in vivo, intravital microscopy was used to study
neutrophil-endothelial cell interactions in single inflamed postcapillary
venules. Superfusion of platelet-activating factor (PAF) (100 nmol/L) onto
the mesentery caused an increase in neutrophil-neutrophil interactions,
neutrophil adhesion to postcapillary venules, and cellular emigration out
of the vasculature. Both L658 758 (an elastase-specific inhibitor), and
Eglin C (an elastase and cathepsin G inhibitor) significantly attenuated
all of these parameters in vivo. To further characterize the mechanism(s)
involved, various in vitro parameters were assessed. HNE, but not trypsin,
caused a dose-dependent (0.01 to 1.0 microgram/mL) increase in the
expression of the beta subunit (CD18) of the CD11/CD18 adhesive
glycoprotein complex on neutrophils. An HNE-dependent increase in CD11b
expression was also observed; however, HNE did not affect the expression of
other neutrophil adhesion molecules (L-selectin), superoxide production, or
degranulation. PAF-enhanced CD18 expression on neutrophils and neutrophil
migration were both abolished by L658 758 but PAF-induced neutrophil
adhesion to endothelial monolayers was not affected by the antiproteinase.
The in vitro data suggest that the antiproteinases do not directly prevent
neutrophil adhesion in vivo but may be important in other CD18-dependent
events such as neutrophil- neutrophil interaction or neutrophil
infiltration (chemotaxis). These results translate into an important,
rate-limiting role for elastase in the process of leukocyte infiltration
and accumulation in inflamed microvessels.
Volume 82,
Issue 7,
pp. 2188-2195,
10/01/1993
Copyright © 1993 by The American Society of Hematology
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