Deficiency of matrix metalloproteinase-13 increases inflammation after acute lung injury.
Human and animal studies of acute lung injury (ALI) have shown that matrix metalloproteinases (MMPs) play an important role in disease pathogenesis, but despite being detected during ALI, the function of the collagenase MMP-13 in ALI is unknown. To evaluate this role of MMP-13, mice deficient in MMP-13 (KO) were examined after hyperoxic lung injury, and compared to wild-type (WT) mice. There was no survival difference between KO and WT mice. There was also no difference in fibrosis between WT and KO mice, as determined by hydroxyproline content and collagen expression by real-time polymerase chain reaction (PCR). Within the bronchoalveolar lavage (BAL), the KO mice exhibited a significant increase in inflammatory cells, when compared to the WT mice (5.51 × 10(5) versus 2.35 × 10(5) cells/mL; P = .001). Increased levels of the chemokine monocyte chemoattractant protein 1 (MCP-1) were observed in the lungs of the KO mice, confirmed via immunohistochemistry. In a subsequent in vitro experiment, MMP-13 was shown to cleave MCP-1. In ALI in the MMP-13 KO mice, MCP-1 could therefore remain active and potentially attract macrophages to the BAL. This study suggests a direct role for MMP-13 in modifying the inflammatory response in the lung after ALI.
Sen
Anita I
AI
Department of Pediatrics, Columbia University, College of Physicians and Surgeons, New York, New York, USA. ais13@columbia.edu
Shiomi
Takayuki
T
Okada
Yasunori
Y
D'Armiento
Jeanine M
JM
D055371:Acute Lung Injury / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D017209:Apoptosis; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018932:Chemokine CCL2 / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D018496:Hyperoxia; D020287:In Situ Nick-End Labeling; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000172:deficiency*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015854:Up-Regulation
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse