Immunohistochemical study of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in pulmonary lymphangioleiomyomatosis (LAM).
To evaluate the role of matrix metalloproteinases (MMPs) and their specific tissue inhibitors (TIMPs) in the pathogenesis of the structural damage and cystic lesions found in pulmonary lymphangioleiomyomatosis (LAM), immunohistochemical studies were made of the localization of MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, TIMP-2, HMB-45, and type IV collagen in sections of lung biopsy specimens from four patients with this disorder. These studies showed increased immunoreactivity compared with that in normal bronchiolar and vascular smooth muscle cells, of MMP-2 and, to a lesser extent, MMP-9 and MMP-1 in the LAM cells. MMP-2 was also localized in some elastic fibers and in the basement membranes of LAM cells and overlying epithelial cells. The basement membranes in both of these sites often showed colocalization of MMP-2 and type IV collagen. Some epithelial basement membranes showing this colocalization were disrupted. These changes were not accompanied by increased immunoreactivity for TIMPs. Taken together with previous observations showing structural damage to elastic fibers and collagen fibrils, and with the absence of demonstrable neutrophil or pancreatic types of elastase, these findings suggest that MMP-2 and MMP-9 (both of which can degrade elastin as well as collagens) are responsible for the connective tissue destruction and cyst formation in LAM.
Hayashi
T
T
Pulmonary-Critical Care Medicine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1518, USA.
Fleming
M V
MV
Stetler-Stevenson
W G
WG
Liotta
L A
LA
Moss
J
J
Ferrans
V J
VJ
Travis
W D
WD
D000328:Adult; D000951:Antigens, Neoplasm; D001706:Biopsy; D003094:Collagen / Q000032:analysis; D017364:Collagenases / Q000032:analysis; D005260:Female; D018093:Gelatinases / Q000032:analysis; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry*; D018192:Lymphangioleiomyomatosis / Q000378:metabolism*; D020781:Matrix Metalloproteinase 1; D020778:Matrix Metalloproteinase 2; D019278:Matrix Metalloproteinase 3 / Q000032:analysis; D020780:Matrix Metalloproteinase 9; D058950:Melanoma-Specific Antigens; D008666:Metalloendopeptidases / Q000032:analysis* / Q000037:antagonists & inhibitors; D009363:Neoplasm Proteins / Q000032:analysis; D011506:Proteins / Q000032:analysis; D019716:Tissue Inhibitor of Metalloproteinase-2; D019714:Tissue Inhibitor of Metalloproteinases
D000951:Antigens, Neoplasm; D006023:Glycoproteins; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D011506:Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D003094:Collagen; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1