Leukocyte protease inhibitor

MA Fath, X Wu, RE Hileman, RJ Linhardt, MA Kashem, RM Nelson, CD Wright, WM Abraham. Interaction of secretary leukocyte protease inhibitor with heparin inhibits protease involved in asthma. J Biol Chem 273 13563— 13569, 1998. 

Wright, C.D., J.A. Kennedy, R.J. Zitnik, and M.A. Kashem. 1999. Inhibition of murine neutrophil serine proteinases by human and murine secretory leukocyte protease inhibitor. Biochem. Biophys. Res. Commun. 254 614—617. 

E. C. Luccy, P. J. Stone. D. EL Ciccolclla, R. Bcuer, T. 0. Christensen, R. C. Thompson, and G- L. Snider. Recombinant human secretory leukocyte-protease inhibitor in vitro properties, and amelioration of human neutrophil elastase-induced emphysema and secretory cell metaplasia in the hamster. /. Lab. Clin. hied. 7/5 224... 

Expression of specific tumor promoter genes Enhanced expression of secretory leukocyte protease inhibitor by TPA Schlingemann et al. [102] Enhanced expression of secretory leukocyte protease inhibitor by TNFa Devoogdt et al. [94]... 

Devoogdt N, Revets H, Kindt A, Liu YQ, De Baetselier P, Ghassabeh GH. The tumor-promoting effects of TNF-a involves the induction of secretory leukocyte protease inhibitor. / Immunol 2006 177 8046-52. 

Similar, but less extensive, studies of secretory leukocyte protease inhibitor (SLPI) have also been performed. Most of the pharmacokinetic evaluation of this material has been performed in animals [235, 236]. In... 

Moriyama, A. Shimoya, K. Ogata, I. Kimura, T. Nakamura, T. Wada, H. Ohashi, K. Azuma, C. Saji, F. Murata, Y. Secretary leukocyte protease inhibitor concentrations in cervical mucus of women with normal menstrual cycle. Mol. Human Reprod. 1999, 5, 665-661. 

Large-Scale Refolding of Secretory Leukocyte Protease Inhibitor... 

A lab-scale procedure for refolding the recombinant protein, secretory leukocyte protease inhibitor, was scaled to 1000 liter production batches. Optimization of reaction conditions by a statistical experimental design approach resulted in consistent activity recoveries of 80-85%, and lowered cost. The statistical design method allows simultaneous optimization of interacting process variables. Changes in the refold reaction conditions greatly influence the level of specific contaminants, thus purity becomes an important parameter in addition to yield. Our experience in the development, scale-up, and cost analysis of a protein refolding operation is presented. 

Secretory leukocyte protease inhibitor is a protein of 11,726 molecular weight, secreted by the parotid gland. First isolated and characterized by Thompson and Ohlsson (7) in 1986, it was found to have a high affinity for leukocyte elastase, cathepsin G and trypsin. The inhibitor is of therapeutic interest in the treatment of disease states that involve leukocyte-mediated proteolysis. Emphysema and cystic fibrosis are examples where severe tissue destruction is caused by uncontrolled proteolytic activity. 

The gene was cloned (2, 5) and expressed in a JM 109 strain of . coli (4). The protein is accumulated intracellularly in an inactive form. Upon cell disruption by high pressure homogenization, recombinant secretory leukocyte protease inhibitor (rSLPI) is only partially soluble, although discrete inclusion bodies have not been identified. Having 16 cysteines involved in 8 intramolecular disulfides, the protein must be refolded to regain full stability and activity. 

SEELY YOUNG Secretory Leukocyte Protease Inhibitor Refolding... 

FEVi forced expiratory volume at 1 second FVC forced vital capacity Pa02 partial pressure of arterial oxygen PaC02 partial pressure of arterial carbon dioxide SLPI secretory leukocyte protease inhibitor UTP uridine triphosphate... 

R. C. Thompson and K. Ohlsson. Isolation, properties and complete amino acid sequence of human leukocyte protease inhibitor, a potent inhibitor of leukocyte elastase. Proc. Natl. Acad. Sci. USA 83 6692 (1986). 

S. W. Harcum, B. E. Dale, and R. J. Seely. Renaturation of recombinant secretory leukocyte protease inhibitor-Aspect of disulfide bond formation kinetics. Biotechnology 75 943 (1993). 

An improved method for enhanced production and biological activity of human secretory leukocyte protease inhibitor (SLPI) in Pichia pastoris. Biochem. Biophys. Res. Common., 402, 519-524. 

Ashcroft, G., Lei, K., and Jin, W. (2000) Secretory leukocyte protease inhibitor mediates non-redundant functions necessary for normal wound healing. Nature Medicine, 6, 1147-1153. 

Baranger, K., Zani, M.L., Labas, V., et al. (2011) Secretory leukocyte protease inhibitor (SLPI) is, hke its homologue tr pin-2 (pre-elafin), a transglutaminase substrate. PLoS One 6, e20976. 

Sallenave, J.M. (2010) Secretory leukocyte protease inhibitor and elafin/trappin-2 versatile mucosal antimicrobials and regulators of immunity. AmerJRespir Cell Mol Biol 42,635-643. 

Schmid, M., Fellermann, K., Fritz, R, etal. (2007) Attenuated induction of epithelial and leukocyte serine antiproteases elafin and secretory leukocyte protease inhibitor in Crohn s disease. J Leukocyte Biol 81, 907-915. 

Seeretory leukocyte protease inhibitor Elafin Colony-stimulating factors G-CSF... 

Abbinante NJ, Simpson LG, Leikauf GD. Corticosteroids increase secretory leukocyte protease inhibitor transcript levels in airway epithelial cells. Am J Physiol 1995 268 1601-1606. 

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