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Insect cell production of a secreted form of human alpha(1)-proteinase inhibitor as a bifunctional protein which inhibits neutrophil elastase and has growth factor-like activities.
- Source :
-
Journal of biotechnology [J Biotechnol] 2002 Jan 31; Vol. 93 (1), pp. 35-44. - Publication Year :
- 2002
-
Abstract
- alpha(1)-proteinase inhibitor (API) is a potential therapeutic agent in all diseases in which elastase released by neutrophils has to be effectively neutralized. We ligated the cDNA of human API to the C-terminal section of an insulin-like growth factor II analogue (BOMIGF), known to be properly folded and secreted in insect cells using the baculovirus expression system. The BOMIGF-API chimera was recovered from the incubation medium of the infected cells. It shared the properties of both IGFs and API. It inhibited neutrophil elastase and formed SDS-stable complexes with the enzyme. The attachment of the large API protein to the C-terminal end of the 10 kDa IGF analogue did not destroy the IGF-mediated stimulation of thymidine incorporation into bovine fetal erythroid cells. We tested the capacity of the chimera to affect fibronectin-dependent TF-1 cell migration. BOMIGF-API significantly restored TF-1 cell migration in the presence of elastase, which is the enzyme of burn wound fluid most probably involved in fibronectin degradation. Some of the beneficial uses for this chimera may include all instances for which inhibition of elastase-mediated extracellular matrix destruction as well as stimulation of cell migration and proliferation are required for tissue repair.
- Subjects :
- Animals
Base Sequence
Biotechnology
Cattle
Cell Line
Cell Movement drug effects
DNA, Complementary genetics
Erythrocytes drug effects
Erythrocytes metabolism
Growth Substances biosynthesis
Growth Substances genetics
Growth Substances pharmacology
Humans
In Vitro Techniques
Moths
Recombinant Fusion Proteins biosynthesis
Recombinant Fusion Proteins genetics
Recombinant Fusion Proteins pharmacology
Thymidine metabolism
alpha 1-Antitrypsin genetics
alpha 1-Antitrypsin metabolism
alpha 1-Antitrypsin pharmacology
Leukocyte Elastase antagonists & inhibitors
alpha 1-Antitrypsin biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 0168-1656
- Volume :
- 93
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of biotechnology
- Publication Type :
- Academic Journal
- Accession number :
- 11690693
- Full Text :
- https://doi.org/10.1016/s0168-1656(01)00380-7