Effect of endothelin-1 on neutrophil adhesion to endothelial cells and perfused heart.
BACKGROUND
Based on recent evidence showing that endothelin-1 stimulates several activation mechanisms on neutrophils, the aim of the present study was to analyze the effects of endothelin-1 on neutrophil adhesion to endothelial cells and neutrophil accumulation in the heart.


RESULTS
The experiments included (1) adhesion of 51Cr-labeled human neutrophils to bovine endothelial cells in culture both in the presence and absence of monoclonal antibodies against the alpha- and beta-subunits of integrins; (2) surface expression of the alpha- and beta-integrin antigens; (3) accumulation of 51Cr-labeled neutrophils on the isolated perfused rabbit heart; (4) in vivo accumulation of autologous neutrophils in the heart, as assessed by myeloperoxidase activity. Endothelin-1 stimulated neutrophil adhesion to endothelial cells (increase of 1 x 10(5) +/- 1 x 10(4) neutrophils per well). The endothelin-1-induced adhesion was blocked (83 +/- 6%) by the anti-CD18 antibody TS1/18 and by several anti-alpha-subunit antibodies. The expression of CD18 and CD11b on the neutrophil surface was also increased by endothelin-1. Endothelin-1 enhanced neutrophil accumulation in the isolated rabbit heart by 4.2 times throughout a TS1/18-inhibitable mechanism. Myeloperoxidase activity increased by 4.2 times in hearts infused in vivo with endothelin-1.


CONCLUSIONS
Endothelin-1 stimulates neutrophil adhesion to endothelial cells by an effect on the expression of adhesive molecules on the neutrophil surface. Endothelin-1 stimulates neutrophil accumulation in vivo and in vitro in the heart. Antibodies against the integrin complex block the endothelin-1-dependent neutrophil adhesion. These findings have potential importance in the pathophysiology of endothelin-1-increased states.
Instituto de Investigaciones Médicas, Fundación Jiménez Díaz, Madrid, Spain.
A
A
López Farré
A
A
Riesco
G
G
Espinosa
E
E
Digiuni
M R
MR
Cernadas
V
V
Alvarez
M
M
Montón
F
F
Rivas
M J
MJ
Gallego
J
J
Egido
D000818:Animals; D002417:Cattle; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology; D002478:Cells, Cultured; D016232:Endothelins / Q000494:pharmacology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology*; D006321:Heart / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D016177:Macrophage-1 Antigen / Q000502:physiology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010477:Perfusion; D009195:Peroxidase / Q000378:metabolism; D011817:Rabbits
D015815:Cell Adhesion Molecules; D016232:Endothelins; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D009195:Peroxidase