The effect of matrix metalloproteinase-3 deficiency on pulmonary surfactant in a mouse model of acute lung injury.
The acute respiratory distress syndrome (ARDS) is characterized by arterial hypoxemia accompanied by severe inflammation and alterations to the pulmonary surfactant system. Published data has demonstrated a protective effect of matrix metalloproteinase-3 (Mmp3) deficiency against the inflammatory response associated with ARDS; however, the effect of Mmp3 on physiologic parameters and alterations to surfactant have not been previously studied. It was hypothesized that Mmp3 deficient (Mmp3(-/-)) mice would be protected against lung dysfunction associated with ARDS and maintain a functional pulmonary surfactant system. Wild type (WT) and Mmp3(-/-) mice were subjected to acid-aspiration followed by mechanical ventilation. Mmp3(-/-) mice maintained higher arterial oxygenation compared with WT mice at the completion of ventilation. Significant increase in functional large aggregate surfactant forms were observed in Mmp3(-/-) mice compared with WT mice. These findings further support a role of Mmp3 as an attractive therapeutic target for drug development in the setting of ARDS.
a Lawson Health Research Institute, Department of Physiology and Pharmacology, Western University, London ON, Canada.|c Department of Medicine, Western University, London ON, Canada.
Cory M
CM
Yamashita
a Lawson Health Research Institute, Department of Physiology and Pharmacology, Western University, London ON, Canada.
Candice
C
Cybulskie
a Lawson Health Research Institute, Department of Physiology and Pharmacology, Western University, London ON, Canada.
Scott
S
Milos
b Department of Mechanical Engineering, University of Hawaii at Manoa, Honolulu, HI, USA.
Yi Y
YY
Zuo
a Lawson Health Research Institute, Department of Physiology and Pharmacology, Western University, London ON, Canada.
Lynda A
LA
McCaig
a Lawson Health Research Institute, Department of Physiology and Pharmacology, Western University, London ON, Canada.|c Department of Medicine, Western University, London ON, Canada.
Ruud A W
RA
Veldhuizen
D055371:Acute Lung Injury / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D005260:Female; D019278:Matrix Metalloproteinase 3 / Q000172:deficiency*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011663:Pulmonary Surfactants / Q000378:metabolism*; D011897:Random Allocation; D012128:Respiratory Distress Syndrome / Q000378:metabolism* / Q000473:pathology
D011663:Pulmonary Surfactants; D019278:Matrix Metalloproteinase 3; C511769:Mmp3 protein, mouse
acid aspiration; acute lung injury; acute respiratory distress syndrome; aspiration d’acide; hypoxemia; hypoxémie; lésion pulmonaire aiguë; matrix metalloproteinase-3; mechanical ventilation; métalloprotéinase matricielle-3; pulmonary surfactant; surfactant pulmonaire; syndrome de détresse respiratoire aiguë; ventilation mécanique