Use of ICAM-1 antibodies and antisense oligonucleotides to inhibit transmigration of neutrophils.
OBJECTIVE
The increase in adhesion molecule expression during the initial phase of inflammation leads to transmigration of neutrophils. Inhibition of this transmigration could decrease inflammatory response and tissue damage.


METHODS
Uptake of fluorescein-labelled oligonucleotides, expression of ICAM-1 and neutrophil migration were studied using the bilayer of epithelial (H292) and endothelial (ECV-304) cell lines and neutrophils from peripheral blood of healthy volunteers.


RESULTS
The inhibition of ICAM-1 expression was time dependent for both cell lines, with inhibition of more than 50% after 48 h. Antisense oligos inhibited transmigration already after 4 h of incubation (6.6 +/- 2.5% versus 18.6 +/- 2.5% inhibition, p < 0.01). Antisense was more effective in preventing fMLP-induced neutrophil migration than ICAM-1 antibodies (88 +/- 3.8% versus 67 +/- 7% inhibition, p = 0.02).


CONCLUSIONS
Antisense oligos cause a decrease in ICAM-1 expression and inhibit transmigration of neutrophils. However the effectiveness of antisense is higher than monoclonal antibodies, neither of them is able to block the migration completely. This suggests the existence of ICAM-1 independent mechanisms that are responsible for migration.
Sadowska
A M
AM
Department of Respiratory Medicine, Antwerp Metabolic Research Unit, University of Antwerp (UIA), Universiteitsplein 1, 2610 Antwerpen-Wilrijk, Belgium. anna.sadowska@ua.ac.be
van Overveld
F J
FJ
Luyten
C
C
Germonpré
P
P
De Backer
W A
WA
D000906:Antibodies / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*
D000906:Antibodies; D016376:Oligonucleotides, Antisense; D018799:Intercellular Adhesion Molecule-1