The serpin alpha1-proteinase inhibitor is a critical substrate for gelatinase B/MMP-9 in vivo. Cell 2000 Sep 01;102(5):647-55
Date
09/28/2000Pubmed ID
11007483DOI
10.1016/s0092-8674(00)00087-8Scopus ID
2-s2.0-0034257889 (requires institutional sign-in at Scopus site) 346 CitationsAbstract
We have identified the key protein substrate of gelatinase B/MMP-9 (GB) that is cleaved in vivo during dermal-epidermal separation triggered by antibodies to the hemidesmosomal protein BP180 (collagen XVII, BPAG2). Mice deficient in either GB or neutrophil elastase (NE) are resistant to blister formation in response to these antibodies in a mouse model of the autoimmune disease bullous pemphigoid. Disease develops upon complementation of GB -/- mice with NE -/- neutrophils or NE -/- mice with GB -/- neutrophils. Only NE degrades BP180 and produces dermal-epidermal separation in vivo and in culture. Instead, GB acts upstream to regulates NE activity by inactivating alpha1-proteinase inhibitor (alpha1-PI). Excess NE produces lesions in GB -/- mice without cleaving alpha1-PI. Excess alpha1-PI phenocopies GB and NE deficiency in wild-type mice.
Author List
Liu Z, Zhou X, Shapiro SD, Shipley JM, Twining SS, Diaz LA, Senior RM, Werb ZAuthor
Sally S. Twining PhD Assistant Dean, Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAnimals, Newborn
Antibodies
Autoantigens
Blister
Cell Adhesion
Dermis
Disease Models, Animal
Epidermis
Leukocyte Elastase
Matrix Metalloproteinase 9
Mice
Mice, Inbred BALB C
Mice, Knockout
Neutrophil Infiltration
Neutrophils
Non-Fibrillar Collagens
Pemphigoid, Bullous
Peroxidase
Protein Processing, Post-Translational
Substrate Specificity
alpha 1-Antitrypsin
