Preparation and properties of a therapeutic inter-alpha-trypsin inhibitor concentrate from human plasma

C. Michalski, F. Piva, M. Balduyck, C. Mizon, T. Burnouf, J. J. Huart, J. Mizon

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Inter-α-trypsin inhibitor (ITI) is a serine protease inhibitor found in human plasma. Its antiprotease activity is due to bikunin which is effective in various types of experimental shock and pancreatitis. Therefore ITI, which releases bikunin by proteolytic cleavage, could be of therapeutic interest. A method for the large-scale isolation of ITI from human plasma is described. ITI was purified from the prothrombin complex concentrate (PCC) by diethylaminoethyl-Sepharose fast-flow chromatography followed by a chromatographic step on immobilized heparin designed to remove C4, factor X and protein C. With this procedure, which was performed under mild conditions, a homogeneous preparation of native ITI was obtained, as demonstrated by electrophoretic and chromatographic analyses. ITI maintained its biological activity, as exhibited by its specific antitryptic activity of 420 ± 65 IU/g. In order to decrease or eliminate the risk of transmission of viral disease due to lipid-enveloped viruses, the process incorporated a solvent-detergent treatment. Animal studies on the final product revealed no adverse side-effects in terms of toxicity, thrombogenicity or hypotension. This preparation appears suitable for therapeutic evaluation in animal experimental models.

Original languageEnglish
Pages (from-to)329-336
Number of pages8
JournalVox Sanguinis
Volume67
Issue number4
Publication statusPublished - 1994
Externally publishedYes

Fingerprint

Trypsin Inhibitors
Chromatography
Therapeutics
Factor X
Serine Proteinase Inhibitors
Virus Diseases
Protein C
Protease Inhibitors
Pancreatitis
Detergents
Hypotension
Sepharose
Heparin
inter-alpha-inhibitor
Shock
Animal Models
Viruses
Lipids

ASJC Scopus subject areas

  • Hematology

Cite this

Michalski, C., Piva, F., Balduyck, M., Mizon, C., Burnouf, T., Huart, J. J., & Mizon, J. (1994). Preparation and properties of a therapeutic inter-alpha-trypsin inhibitor concentrate from human plasma. Vox Sanguinis, 67(4), 329-336.

Preparation and properties of a therapeutic inter-alpha-trypsin inhibitor concentrate from human plasma. / Michalski, C.; Piva, F.; Balduyck, M.; Mizon, C.; Burnouf, T.; Huart, J. J.; Mizon, J.

In: Vox Sanguinis, Vol. 67, No. 4, 1994, p. 329-336.

Research output: Contribution to journalArticle

Michalski, C, Piva, F, Balduyck, M, Mizon, C, Burnouf, T, Huart, JJ & Mizon, J 1994, 'Preparation and properties of a therapeutic inter-alpha-trypsin inhibitor concentrate from human plasma', Vox Sanguinis, vol. 67, no. 4, pp. 329-336.
Michalski, C. ; Piva, F. ; Balduyck, M. ; Mizon, C. ; Burnouf, T. ; Huart, J. J. ; Mizon, J. / Preparation and properties of a therapeutic inter-alpha-trypsin inhibitor concentrate from human plasma. In: Vox Sanguinis. 1994 ; Vol. 67, No. 4. pp. 329-336.
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