Epinephrine as a mediator of pulmonary neutrophil sequestration.
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.
Morken
Jeffrey J
JJ
Hennepin County Medical Center, Minneapolis, Minnesota 55404, USA.
Warren
Krista U
KU
Xie
Yonghong
Y
Rodriguez
Jorge L
JL
Lyte
Mark
M
D000818:Animals; D001998:Bronchopulmonary Sequestration / Q000503:physiopathology; D004837:Epinephrine / Q000494:pharmacology*; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009504:Neutrophils / Q000187:drug effects*; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D018805:Sepsis / Q000503:physiopathology; D013154:Spleen / Q000187:drug effects / Q000201:enzymology; D013997:Time Factors; D014947:Wounds and Injuries / Q000503:physiopathology
D009195:Peroxidase; D004837:Epinephrine