title: Epinephrine enhances platelet-neutrophil adhesion in whole blood in vitro.
abstract: Previous studies showed that alpha- or beta-adrenoceptor stimulation by catecholamines influenced neutrophil function, cytokine liberation, and platelet aggregability. We investigated whether adrenergic stimulation with epinephrine also alters platelet-neutrophil adhesion. This might be of specific interest in the critically ill, because the increased association of platelets and neutrophils has been shown to be of key importance in inflammation and thrombosis. For this purpose, whole blood was incubated with increasing concentrations of epinephrine (10 nM, 100 nM, and 1 microM). To distinguish receptor-specific effects, a subset of samples was incubated with propranolol (10 microM) or phentolamine (10 microM) before exposure to epinephrine. After incubation, another subset of samples was also stimulated with 100 nM of N-formyl-methionyl-leucyl-phenylalanine. All samples were stained, and platelet-neutrophil adhesion and CD45, L-selectin, CD11b, P-selectin glycoprotein ligand-1, glycoprotein IIb/IIIa, and P-selectin expression were measured by two-color flow cytometry. Epinephrine significantly enhanced platelet-neutrophil adhesion and P-selectin and glycoprotein IIb/IIIa expression on platelets. CD11b and L-selectin expression on unstimulated neutrophils remained unchanged, whereas N-formyl-methionyl-leucyl-phenylalanine-induced upregulation of CD11b and downregulation of L-selectin were suppressed by epinephrine. beta-Adrenergic blockade before incubation with epinephrine increased platelet-neutrophil aggregates and adhesion molecule expression (CD11b, P-selectin, and glycoprotein IIb/IIIa) even further. These results demonstrate that epinephrine enhances platelet-neutrophil adhesion. The alpha-adrenergic receptor-mediated increase in P-selectin and glycoprotein IIb/IIIa expression on platelets may contribute substantially to this effect. Our study shows that inotropic support enhances the platelet-neutrophil interaction, which might be crucial for critically ill patients.
authors.affiliation: *Department of Anesthesiology, Rheinisch-Westfälische Technische Hochschule, Aachen, Germany; †Department of Anesthesiology, Spitalul Clinic de Ortopedie Foisor, Bucuresti, Romania; and ‡Institute of Transfusion Medicine, Rheinisch-Westfälische Technische Hochschule, Aachen, Germany.
authors.forename: Nicola A
authors.initials: NA
authors.lastname: Horn
authors.forename: Denisa M
authors.initials: DM
authors.lastname: Anastase
authors.forename: Klaus E
authors.initials: KE
authors.lastname: Hecker
authors.forename: Jan H
authors.initials: JH
authors.lastname: Baumert
authors.forename: Tilo
authors.initials: T
authors.lastname: Robitzsch
authors.forename: Rolf
authors.initials: R
authors.lastname: Rossaint
mesh_terms: D000322:Adrenergic Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D039481:CD11b Antigen / Q000096:biosynthesis; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D048429:Cell Size; D004837:Epinephrine / Q000494:pharmacology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D066298:In Vitro Techniques; D019041:L-Selectin / Q000096:biosynthesis; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects*; D010973:Platelet Adhesiveness / Q000187:drug effects*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000187:drug effects
chemical_list: D000322:Adrenergic Agonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D039481:CD11b Antigen; D015815:Cell Adhesion Molecules; D007155:Immunologic Factors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019041:L-Selectin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D004837:Epinephrine