© 1997 American Heart Association, Inc.
Articles |
Transendothelial Neutrophil Migration
Role of Neutrophil-Derived Proteases and Relationship to Transendothelial Protein Movement
From the Division of Vascular Biology, London Health Sciences Centre-Research, London, Ontario, Canada N6A 4G5.
Correspondence to Peter R. Kvietys, PhD, LHSC-Research, 375 South St, Room C206, London, Ontario, Canada N6A 4G5. E-mail pkvietys{at}julian.uwo.ca
Abstract During an acute inflammatory response
polymorphonuclear leukocytes (PMNs) adhere to and emigrate across
the venular microvasculature. There is general agreement on the
mechanisms involved in PMN adhesive interactions. However, the
mechanisms by which PMNs migrate across the endothelial
lining remain controversial, particularly with respect to the role of
elastase. In the present study, we used human umbilical vein
endothelial cells (HUVECs) and PMNs to test the
hypothesis that the relative role of PMN-derived elastase may be
dependent on the degree of HUVEC retraction within monolayers. A high
(10-7 mol/L), but not a low
(10-10 mol/L), concentration of
platelet-activating factor (PAF) caused HUVEC retraction of
sufficient magnitude to increase transendothelial
protein movement. Elastase inhibitors prevented PMN
transendothelial migration in response to the low, but
not the high, concentration of PAF. These findings suggest that PMN
migration across confluent endothelial cells is
elastase dependent, whereas PMN migration across retracted
endothelial cells is elastase independent. However,
under the latter condition (high concentration of PAF), the two
endogenous proteases, 
2-macroglobulin and
1-antitrypsin, could interfere with PAF-induced PMN
transendothelial migration. Thus, as the concentration
of PAF is increased, migrating PMNs use other proteases, in addition to
elastase. We also noted that transendothelial
protein movement is closely coupled to PMN migration.
Key Words: elastase • 2-macroglobulin • 1-antitrypsin
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