Endothelin-1-induced PMN infiltration and mucosal dysfunction in the rat small intestine.
The objectives of this study were to characterize the effects of endothelin (ET)-1 on intestinal mucosal parameters and to assess the contribution of polymorphonuclear leukocytes (PMNs), intercellular adhesion molecule-1 (ICAM-1), and a platelet-activating factor (PAF) to the mucosal dysfunction induced by ET-1. Different concentrations of ET-1 (100, 200, and 400 pmol/kg) were infused into the superior mesenteric artery for 10 min, and tissue samples were obtained 30 min after terminating the infusion. ET-1 administration significantly elevated tissue myeloperoxidase activity, plasma carbonyl content, and tissue chemiluminescence intensity, indicating that ET-1 produces PMN infiltration and oxidant stress. Blood-to-lumen clearance of (51)Cr-EDTA significantly increased after ET-1 infusion (400 pmol/kg). Monoclonal antibodies against ICAM-1 (1A29, 2 mg/kg), antineutrophil serum, and PAF antagonist (WEB-2086, 10 mg/kg) attenuated the mucosal barrier dysfunction induced by ET-1. Overall, our data indicate that ET-1 causes PMN accumulation, oxidant stress, and mucosal dysfunction in the rat small intestine and that ET-1-induced mucosal dysfunction involves a mechanism that includes a role for PMNs, ICAM-1, and PAF.
Oktar
B K
BK
Department of Physiology, Marmara University School of Medicine, 81326 Haydarpaşa, Istanbul, Turkey.
Coşkun
T
T
Bozkurt
A
A
Yegen
B C
BC
Yüksel
M
M
Haklar
G
G
Bilsel
S
S
Aksungar
F B
FB
Cetinel
U
U
Granger
D N
DN
Kurtel
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D019332:Endothelin-1 / Q000097:blood / Q000494:pharmacology*; D005260:Female; D007269:Injections, Intra-Arterial; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D007421:Intestine, Small / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008163:Luminescent Measurements; D008297:Male; D009336:Necrosis; D009504:Neutrophils / Q000166:cytology* / Q000201:enzymology; D018384:Oxidative Stress / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014230:Triazoles / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D001381:Azepines; D019332:Endothelin-1; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D014230:Triazoles; C052518:WEB 2086; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase