Inhibition of polymorphonuclear leukocyte-mediated endothelial cell detachment by antileukoprotease: a comparison with other proteinase inhibitors.
The role of elastase and proteinase inhibitors in polymorphonuclear leukocyte(PMN)-mediated injury to human umbilical cord venous endothelial cells (HUVEC) was investigated. Both purified human neutrophil elastase and PMN that were stimulated with serum-treated zymosan (STZ) induced detachment, but not lysis of HUVEC. PMN-, but not purified elastase-mediated detachment was enhanced by the presence of methionine, which indicates a role for reactive oxygen metabolites in PMN-mediated HUVEC detachment. Detachment of HUVEC could be inhibited by secretory leukocyte proteinase inhibitor or antileukoprotease (ALP), alpha 1-proteinase inhibitor (alpha 1-PI) and N-methoxy-succinyl-ala-ala-pro-val-chloromethyl ketone (CMK). At concentrations at which elastase-mediated detachment was maximally inhibited, ALP and CMK, but not alpha 1-PI, were also able to inhibit maximally PMN-mediated detachment. An explanation for this difference could be that the larger size of alpha 1-PI reduces the access of alpha 1-PI to the interface between the PMN and the HUVEC.
Hiemstra
P S
PS
Dept. of Rheumatology, University Hospital Leiden, The Netherlands.
Kramps
J A
JA
de Vreede
T M
TM
Breedveld
F C
FC
Daha
M R
MR
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D009504:Neutrophils / Q000502:physiology*; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000494:pharmacology; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D014471:Umbilical Veins / Q000187:drug effects*; D015054:Zymosan / Q000494:pharmacology; D000515:alpha 1-Antitrypsin / Q000494:pharmacology
D000590:Amino Acid Chloromethyl Ketones; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin; C026704:methoxysuccinyl-alanyl-alanyl-prolyl-valine chloromethyl ketone; D015054:Zymosan; D010196:Pancreatic Elastase