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.

Prevention of Neutrophil Extravasation by α2-Adrenoceptor–Mediated Endothelial Stabilization

“…Nonetheless, when UK14304-pretreated human neutrophils were activated with IL-8, a chemokine widely implicated in neutrophil activation during the adhesion cascade (46), these cells reduced sensitivity to this chemokine in terms of L-selectin shedding and increased CD11b expression. This finding is consistent with the response of L-selectin and CD11b, which has been observed when neutrophils are activated with fMLP in the presence of epinephrine (62). Thus, our data suggest that signaling via the a2-adrenoceptor renders neutrophils less sensitive to proinflammatory mediators.…”

Propranolol Does Not Increase Inflammation, Sepsis, or Infectious Episodes in Severely Burned Children

“…For example, it has been recently shown that epinephrine enhances platelet-neutrophil adhesion, which is crucial for survival of critically ill patients. 26 Ortega et al 27 showed that Norepinephrine stimulated phagocytosis induced by moderate exercise. Garcia et al 28 showed in 2003 that noradrenaline modulates the phagocytic process of macrophages and maintains the phagocytic functions at physiologically optimal levels.…”

Experimental examination of anti-inflammatory effects of a 5-HT3 receptor antagonist, tropisetron, and concomitant effects on autonomic nervous function in a rat sepsis model

“…Sympathetic overstimulation in an LPS-induced sepsis model reportedly lead to sympathetic-vagal disequilibrium [39]. Furthermore, almost all immunocompetent cells have adrenergic receptors [40], and catecholamines exhibit substantial immunomodulatory effects [41][42][43][44]. Considering this close relationship between the autonomic nervous system and immune response, there may be two alternative explanations for the inhibitory effect of tropisetron on induction of both cytokines and catecholamines observed in the present study: 1) tropisetron modulated autonomic nervous activity to inhibit cytokine production; or 2) tropisetron inhibited cytokine production to modulate autonomic nervous activity and thereby inhibit catecholamine induction.…”