The Role of Cystathionine-γ-Lyase In Blunt Chest Trauma in Cigarette Smoke Exposed Mice.
Pretraumatic cigarette smoke (CS) exposure aggravates posttraumatic acute lung injury (ALI). Cystathionine-γ-lyase (CSE) protects against ALI and CS exposure-induced chronic obstructive lung disease (COPD). Therefore, we tested the hypothesis whether genetic CSE knockout (CSE) would aggravate posttraumatic ALI after CS exposure. After 3 to 4 weeks of CS exposure, anesthetized wild-type (WT) and CSE mice underwent blunt chest trauma, surgical instrumentation and 4 h of lung-protective mechanical ventilation. We measured hemodynamics, lung mechanics, gas exchange, metabolism, and acid-base status together with blood and tissue cytokine and chemokine levels, tissue expression of mediator proteins, parameters of oxidative and nitrosative stress, and histology. CSE mice without CS exposure showed higher cytokine and chemokine levels, and this was further enhanced by CS exposure, particularly in males. CS exposure in WT mice aggravated posttraumatic alveolar membrane thickening, dystelectasis, and inflammatory cell accumulation, which was associated with higher thoracopulmonary compliance. Pretraumatic CS exposure in CSE mice produced a similar response, except for less alveolar membrane thickening, most likely due to lung hyperinflation. CS-exposed WT mice showed the most pronounced metabolic acidosis, while CS exposure in CSE mice resulted in the lowest blood glucose levels. Urinary output and anesthesia rate were highest in male CS-exposed CSE animals. In conclusion, in murine acute-on-chronic pulmonary disease, CSE knockout aggravated posttraumatic inflammation, which was further worsened upon pretraumatic CS exposure, and this effect was particularly pronounced in males. Hence, maintaining CSE expression is critically important for stress adaptation during ALI and CS-induced COPD, most likely in a gender-dependent manner.
*Institute of Anesthesiological Pathophysiology and Process Engineering, University Hospital, Ulm, Germany †Department of Anesthesiology, University Hospital, Ulm, Germany ‡Institute of Pathology, University Hospital, Ulm, Germany §Department of Traumatology, Hand, Plastic- and Reconstructive Surgery, University Hospital, Ulm, Germany ||Department of Pulmonary Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany ¶Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas #Department of Biology, Laurentian University, Sudbury, Canada.
Clair
C
Hartmann
Sebastian
S
Hafner
Angelika
A
Scheuerle
Peter
P
Möller
Markus
M
Huber-Lang
Birgit
B
Jung
Benedikt
B
Nubaum
Oscar
O
McCook
Michael
M
Gröger
Florian
F
Wagner
Sandra
S
Weber
Bettina
B
Stahl
Enrico
E
Calzia
Michael
M
Georgieff
Csaba
C
Szabó
Rui
R
Wang
Peter
P
Radermacher
Katja
K
Wagner
D055371:Acute Lung Injury / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D000818:Animals; D018925:Chemokines / Q000378:metabolism; D000073865:Cigarette Smoking / Q000009:adverse effects*; D020552:Comet Assay; D003542:Cystathionine gamma-Lyase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D015151:Immunoblotting; D008168:Lung / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D013898:Thoracic Injuries / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism*; D014949:Wounds, Nonpenetrating / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism
D018925:Chemokines; D016207:Cytokines; D003542:Cystathionine gamma-Lyase