Peptides derived from the lectin domain of selectin adhesion molecules inhibit leukocyte rolling in vivo.
OBJECTIVE
The selectins are a family of adhesion molecules that mediate leukocyte rolling, a prerequisite for their later firm adhesion and migration to sites of inflammation. The N-terminal lectin domain of selectins is important for Ca(2+)-dependent binding to oligosaccharide ligands. We set out to study the effect of peptides corresponding to residues 11-20, 23-30, 36-50, 54-63, 70-79 and 109-118 (counting from the N-terminus of the mature proteins) of the lectin domain of human L-, P- and E-selectins on leukocyte rolling in vivo.


METHODS
Peptides were applied by local intravascular microinfusion via a glass micropipette into rat mesenteric venules. Visibly rolling cells were counted off-line and compared with rolling cells counted during control periods.


RESULTS
Peptides corresponding to residues 70-79 of P-selectin and 11-20 of L-selectin reduced leukocyte rolling flux in rat mesenteric venules to less than 30% of that measured during control infusion. Peptides corresponding to residues 109-118 of P-selectin, 54-63 of L-selectin and 23-30 of E-selectin also reduced leukocyte rolling flux, although to a lesser degree.


CONCLUSIONS
We have shown that small peptides based on the lectin domain of all three selectins can be effective inhibitors of leukocyte rolling in vivo.
Norman
K E
KE
Department of Biomedical Engineering, University of Virginia, Charlottesville, USA.
Scheding
C
C
Kunkel
E J
EJ
Heavner
G A
GA
Ley
K
K
D000595:Amino Acid Sequence; D000818:Animals; D019040:E-Selectin / Q000737:chemistry; D005260:Female; D019041:L-Selectin / Q000737:chemistry; D037102:Lectins / Q000737:chemistry*; D007962:Leukocytes / Q000187:drug effects*; D008969:Molecular Sequence Data; D019007:P-Selectin / Q000737:chemistry; D010455:Peptides / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D019087:Selectins / Q000737:chemistry*
D019040:E-Selectin; D037102:Lectins; D019007:P-Selectin; D010455:Peptides; D019087:Selectins; D019041:L-Selectin