Epinephrine as a Mediator of Pulmonary Neutrophil Sequestration

Abstract

Neutrophil-mediated lung injury is a potential complication of trauma and sepsis. Concomitant with trauma and sepsis, there is an immediate and sustained systemic elevation of catecholamines including epinephrine. In the absence of trauma or sepsis, we examined whether epinephrine contributes to the accumulation of neutrophils in the lung. Eight- to 12-week-old male CF-1 mice were injected i.p. with 0.2 mL of normal saline or epinephrine (0.1-5.0 mg/kg). An unmanipulated control group was included to examine the stress of i.p. injection. Animals were sacrificed at predetermined time points, and lung and spleen were harvested. PMN accumulation was assessed by using a myeloperoxidase (MPO) assay, which is an indirect marker for neutrophil presence. Morphometric analysis of lung tissue was performed by a pathologist blinded to the groups. Increasing epinephrine doses resulted in a significantly increased accumulation of pulmonary neutrophils compared with normal saline. The stress of normal saline injection also resulted in a significantly greater pulmonary neutrophil accumulation than unmanipulated controls. The effects of epinephrine on pulmonary neutrophil accumulation were greatest at 2 h, but they were not significantly different from saline-injected controls by 12 h. These results correlated with histological analysis. There were no significant differences in spleen MPO activity between groups, suggesting an organ-specific mechanism of epinephrine-induced pulmonary neutrophil sequestration. In the absence of trauma, shock, or infection, epinephrine results in the accumulation of neutrophils in murine lungs. The finding that "injection stress" increased lung neutrophil sequestration suggests the possibility that this mechanism may be physiologically relevant. Thus, epinephrine release in trauma may set the stage for development of neutrophil-mediated acute lung injury.

Desensitization of β‐adrenergic receptors in lung injury induced by 2‐chloroethyl ethyl sulfide, a mustard analog

“…Zang et al [55] have shown that oxygen radicals play an important role in the nonvagal component of the noncholinergic bronchoconstriction in guinea pigs in vivo . Morken et al [56] have shown that there is an immediate and sustained systemic elevation of catecholamines including epinephrine, which may set the stage for development of neutrophils-mediated acute lung injury. Furthermore, it has been reported that stress and hypoxia of anaphylaxis cause catecholamine release, loss of choline-containing phospholipids, and thereby ARDS [57].…”

Intravenous Arginine Vasopressin in Critically Ill Children: Is It Beneficial?

“…An additional important benefit of vasopressin therapy, observed by us and others (9,11), was its ability to decrease the need for catecholamine agonists, especially the epinephrine dose. This results in a potential reduction in adverse effects of epinephrine on the cardiovascular system such as severe arrhythmia and increased myocardial oxygen consumption, resulting in a severe mismatch of cardiac oxygen delivery (1,(15)(16)(17)(18).…”

Catecholamine Stress Alters Neutrophil Trafficking and Impairs Wound Healing by β 2 -Adrenergic Receptor–Mediated Upregulation of IL-6

“…These elevated levels of epinephrine can result in enhanced release of pro-inflammatory cytokines including tumor necrosis factor-α (TNFα), interleukin (IL)-1β, and IL-6 (Frost et al , 2004; Johnson et al , 2005; Wong et al , 2012). Since these cytokines can recruit PMNs to the site of inflammation, their generation as a result of catecholamine stress could provide a link to the observed increase in PMN trafficking to the lung and liver of mice that have been challenged with high doses of epinephrine (Morken et al , 2002; von Montfort et al , 2008). Additionally, extraneuronal generation of epinephrine within the wound by PMNs themselves provides a potential for amplification of the catecholamine-mediated inflammatory response (Flierl et al , 2007).…”