Differential role of selectins in experimental colitis.
OBJECTIVE
The role of selectins in experimental colitis remains unknown. The aims of this study were to characterize the time-course expression of selectins in trinitrobenzene sulfonic acid (TNBS)-induced colitis, the functional role of selectins in colonic leukocyte-endothelial cell interactions, and the therapeutic usefulness of selectin blockade in this model.


METHODS
Control and TNBS-induced colitic rats were studied. Expression of P- and E-selectin was assessed by the radiolabeled antibody technique, and L-selectin by flow cytometry. Leukocyte-endothelial cell interactions were studied in colonic venules by using intravital microscopy under basal conditions and after P-, E-, or L-selectin immunoblockade. Additional groups of animals were treated with anti-P-selectin antibody, a nonbinding antibody, or dexamethasone, for 7 days.


RESULTS
P-selectin and E-selectin expression were markedly up-regulated in colitic rats. Increased leukocyte rolling was abrogated by anti-P-selectin, but only attenuated by anti-E- or anti-L-selectin antibodies. Only pretreatment with anti-P- selectin decreased leukocyte adhesion. Animals chronically treated with dexamethasone, but not with anti- P-selectin, had significantly lower macroscopic and histologic damage scores, colon weight, and myeloperoxidase (MPO) activity than those treated with nonbinding antibody.


CONCLUSIONS
P-selectin plays a key role on leukocyte rolling and its blockade attenuates leukocyte adhesion in TNBS-induced colitis. However, treatment with an anti-P-selectin antibody does not significantly improve colitis.
Department of Gastroenterology, Institut de Malalties Digestives, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Catalonia, Spain.
M
M
Sans
A
A
Salas
A
A
Soriano
N
N
Prats
M
M
Gironella
P
P
Pizcueta
M
M
Elena
D C
DC
Anderson
J M
JM
Piqué
J
J
Panés
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001835:Body Weight; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D019040:E-Selectin / Q000276:immunology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D019041:L-Selectin / Q000276:immunology / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D019007:P-Selectin / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019087:Selectins / Q000276:immunology / Q000378:metabolism*; D014302:Trinitrobenzenesulfonic Acid; D014699:Venules / Q000378:metabolism
D000911:Antibodies, Monoclonal; D019040:E-Selectin; D019007:P-Selectin; D019087:Selectins; D019041:L-Selectin; D014302:Trinitrobenzenesulfonic Acid