Cocaine and catecholamines enhance inflammatory cell retention in the coronary circulation of mice by upregulation of adhesion molecules.
Cocaine treatment of mice with viral myocarditis significantly increases neutrophil infiltration into the myocardium and exacerbates the inflammatory response. The mechanisms of these effects are unknown; however, it may be that cocaine increases circulating catecholamines and consequently increases inflammatory cell adhesion to the coronary endothelium. Here, we examined the hypothesis that cocaine enhances inflammatory cell infiltration via catecholamine-induced upregulation of cell adhesion molecule (CAM) expression in adult BALB/c mouse hearts. Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), endothelial leukocyte adhesion molecule-1 (E-selectin), and leukocyte adhesion molecule-1 (L-selectin) were detected by gene array analysis, RT-PCR, Western blotting, and immunohistochemical staining. CAMs were significantly upregulated in cocaine-treated mouse hearts. beta-Adrenergic stimulation with epinephrine also upregulated CAM expression, confirming the effects obtained with cocaine. Beta-adrenergic blockade with propranolol inhibited epinephrine-induced CAM expression. In hearts infused with polymorphonuclear neutrophils (PMN), an increased adhesion of PMN to the coronary endothelium was observed in cocaine-treated and epinephrine-treated mouse hearts compared with control hearts. Blocking antibodies against ICAM-1, E-selectin, and L-selectin significantly inhibited epinephrine-enhanced PMN adhesion, whereas anti-VCAM-1 had lesser effects. Our findings suggest that cocaine-induced neutrophil infiltration is mediated by beta-adrenergic stimulation through upregulation of CAM expression, which enhances PMN adhesion. Conversely, beta-adrenergic blockade with propranolol inhibits the effects of cocaine and epinephrine on CAM expression and decreases PMN adhesion to the coronary endothelium. These observations may be of significance for the development of preventative and therapeutic approaches to patients with cocaine- or catecholamine-induced myocarditis.
Chen
Yu
Y
Cardiovascular Division, Department of Medicine, The Charles A. Dana Research Institute and Harvard-Thorndike Laboratories, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Ke
Qingen
Q
Xiao
Yong-Fu
YF
Wu
Guifu
G
Kaplan
Emel
E
Hampton
Thomas G
TG
Malek
Sohail
S
Min
Jiang-Yong
JY
Amende
Ivo
I
Morgan
James P
JP
D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003042:Cocaine / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D019040:E-Selectin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D019041:L-Selectin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000276:immunology* / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D016207:Cytokines; D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin; D011433:Propranolol; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D003042:Cocaine; D004837:Epinephrine