Cromolyn ameliorates acute and chronic injury in a rat lung transplant model.
BACKGROUND
Mast cells have been associated with obliterative bronchiolitis (OB) in human pulmonary allografts, although their role in the development of OB remains unknown.


METHODS
In this study, we evaluated the role of mast cells in pulmonary allograft rejection using an orthotopic rat pulmonary allograft model that utilizes chronic aspiration of gastric fluid to reliably obtain OB. Pulmonary allograft recipients (n = 35) received chronic aspiration of gastric fluid with (n = 10) and without (n = 16) treatment with a mast cell membrane stabilizer, cromolyn sodium, or chronic aspiration with normal saline (n = 9) as a control.


RESULTS
The acute graft injury associated with long ischemic time in the model (6 hours total ischemic time; typical acute graft injury rate ~30%) was apparently blocked by cromolyn, because peri-operative mortality associated with the acute graft injury was not observed in any of the animals receiving cromolyn (p = 0.045). Further, the rats receiving cromolyn developed significantly fewer OB lesions than those treated with gastric fluid alone (p < 0.001), with a mean reduction of 46% of the airways affected.


CONCLUSIONS
These findings provide impetus for further studies aimed at elucidating the effects of cromolyn and the role of mast cells in pulmonary allotransplantation.
Department of Surgery, Duke University Medical Center, Durham, North Carolina; Department of Pathology, Duke University Medical Center, Durham, North Carolina; Department of Surgery, Tzu Chi General Hospital, Hualien, Taiwan.
Jui-Chih
JC
Chang
Department of Surgery, Duke University Medical Center, Durham, North Carolina.
Jason
J
Leung
Department of Surgery, Duke University Medical Center, Durham, North Carolina; Department of Thoracic and Cardiovascular Surgery, The Second Xiangya Hospital, Changsha City, Hunan province, People's Republic of China.
Tao
T
Tang
Department of Surgery, Duke University Medical Center, Durham, North Carolina.
Zoie E
ZE
Holzknecht
Department of Surgery, Duke University Medical Center, Durham, North Carolina.
Matthew G
MG
Hartwig
Department of Surgery, Duke University Medical Center, Durham, North Carolina.
R
R
Duane Davis
Department of Surgery, Duke University Medical Center, Durham, North Carolina.
William
W
Parker
Department of Pathology, Duke University Medical Center, Durham, North Carolina; Departments of Immunology, Duke University Medical Center, Durham, North Carolina; Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina.
Soman N
SN
Abraham
Department of Surgery, Duke University Medical Center, Durham, North Carolina; Department of Pathology, Duke University Medical Center, Durham, North Carolina; Departments of Immunology, Duke University Medical Center, Durham, North Carolina. Electronic address: Shu.Lin@duke.edu.
Shu S
SS
Lin
D055371:Acute Lung Injury / Q000503:physiopathology / Q000517:prevention & control*; D064591:Allografts; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001989:Bronchiolitis Obliterans / Q000473:pathology / Q000503:physiopathology; D018925:Chemokines / Q000378:metabolism; D004205:Cromolyn Sodium / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000473:pathology / Q000503:physiopathology; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D055370:Lung Injury / Q000503:physiopathology / Q000517:prevention & control*; D016040:Lung Transplantation; D008297:Male; D008407:Mast Cells / Q000473:pathology; D011183:Postoperative Complications / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D011921:Rats, Inbred WKY
D018927:Anti-Asthmatic Agents; D018925:Chemokines; D016207:Cytokines; D004205:Cromolyn Sodium
aspiration; gastric fluid; mast cells; obliterative bronchiolitis; pulmonary allograft