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Previous Volume 346:45-53 January 3, 2002 Number 1 Next

	Since this article has no abstract, we have provided an extract of the first 100 words of the full text and any section headings.

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Many biologic processes require a balance between the proteases that initiate the proteolytic pathways essential to life and the inhibitors that limit excessive protease activity. There are many different families of protease inhibitors, but of these just one exceptional family of serine protease inhibitors, the serpins, appears to control the key intracellular and extracellular pathways.¹ Among the serpins, alpha₁-antitrypsin protects the connective tissue of the lungs from the elastase released by leukocytes, antithrombin ensures the efficient destruction of released coagulation proteases, C1 inhibitor controls complement activation, and the inhibitors of plasmin and its activators control fibrinolysis. The role of . . . [Full Text of this Article]

Inactivation, Thrombosis, and Hemorrhage

Alpha₁-Antitrypsin Deficiency and Conformational Instability

Polymerization and Cirrhosis

Alpha₁-Antitrypsin Deficiency and Emphysema

Neuroserpin and the Conformational Dementias

Prospects for Therapy

Source Information

From the Departments of Hematology and Medicine, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, United Kingdom.

Address reprint requests to Dr. Carrell at the Departments of Hematology and Medicine, University of Cambridge, Cambridge Institute for Medical Research, Hills Rd., Cambridge CB2 2XY, United Kingdom, or at rwc1000@cam.ac.uk.

References

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• Adler, K. B., Matalon, S. (2009). Highlights of the November Issue. Am. J. Respir. Cell Mol. Bio. 41: 505-506 [Full Text]  
• Lazrak, A., Nita, I., Subramaniyam, D., Wei, S., Song, W., Ji, H.-L., Janciauskiene, S., Matalon, S. (2009). {alpha}1-Antitrypsin Inhibits Epithelial Na+ Transport In Vitro and In Vivo. Am. J. Respir. Cell Mol. Bio. 41: 261-270 [Abstract] [Full Text]  
• Silverman, E. K., Sandhaus, R. A. (2009). Alpha1-Antitrypsin Deficiency. NEJM 360: 2749-2757 [Full Text]  
• Hubner, R. H., Leopold, P. L., Kiuru, M., De, B. P., Krause, A., Crystal, R. G. (2009). Dysfunctional Glycogen Storage in a Mouse Model of {alpha}1-Antitrypsin Deficiency. Am. J. Respir. Cell Mol. Bio. 40: 239-247 [Abstract] [Full Text]  
• Ramadas, R. A., Wu, L., LeVine, A. M. (2009). Surfactant Protein A Enhances Production of Secretory Leukoprotease Inhibitor and Protects It from Cleavage by Matrix Metalloproteinases. J. Immunol. 182: 1560-1567 [Abstract] [Full Text]  
• Janciauskiene, S., Nita, I., Subramaniyam, D., Li, Q., Lancaster, J. R. Jr., Matalon, S. (2008). {alpha}1-Antitrypsin Inhibits the Activity of the Matriptase Catalytic Domain In Vitro. Am. J. Respir. Cell Mol. Bio. 39: 631-637 [Abstract] [Full Text]  
• Prins, J., van der Meijden, B. B., Kraaijenhagen, R. J., Wielders, J. P.M. (2008). Inherited Chronic Obstructive Pulmonary Disease: New Selective-Sequencing Workup for {alpha}1-Antitrypsin Deficiency Identifies 2 Previously Unidentified Null Alleles. Clin. Chem. 54: 101-107 [Abstract] [Full Text]  
• Scott, C. M., Kruse, K. B., Schmidt, B. Z., Perlmutter, D. H., McCracken, A. A., Brodsky, J. L. (2007). ADD66, a Gene Involved in the Endoplasmic Reticulum-associated Degradation of {alpha}-1-Antitrypsin-Z in Yeast, Facilitates Proteasome Activity and Assembly. Mol. Biol. Cell 18: 3776-3787 [Abstract] [Full Text]  
• Grupe, A., Abraham, R., Li, Y., Rowland, C., Hollingworth, P., Morgan, A., Jehu, L., Segurado, R., Stone, D., Schadt, E., Karnoub, M., Nowotny, P., Tacey, K., Catanese, J., Sninsky, J., Brayne, C., Rubinsztein, D., Gill, M., Lawlor, B., Lovestone, S., Holmans, P., O'Donovan, M., Morris, J. C., Thal, L., Goate, A., Owen, M. J., Williams, J. (2007). Evidence for novel susceptibility genes for late-onset Alzheimer's disease from a genome-wide association study of putative functional variants. Hum Mol Genet 16: 865-873 [Abstract] [Full Text]  
• Janciauskiene, S. M., Nita, I. M., Stevens, T. (2007). {alpha}1-Antitrypsin, Old Dog, New Tricks: {alpha}1-ANTITRYPSIN EXERTS IN VITRO ANTI-INFLAMMATORY ACTIVITY IN HUMAN MONOCYTES BY ELEVATING cAMP. J. Biol. Chem. 282: 8573-8582 [Abstract] [Full Text]  
• Harb, R., Thomas, D. W. (2007). Conjugated Hyperbilirubinemia: Screening and Treatment in Older Infants and Children. Pediatr. Rev. 28: 83-91 [Full Text]  
• Kaczor, M. P., Sanak, M., Szczeklik, A. (2007). Rapid and Inexpensive Detection of {alpha}1-Antitrypsin Deficiency-Related Alleles S and Z by a Real-Time Polymerase Chain Reaction Suitable for a Large-Scale Population-Based Screening. J. Mol. Diagn. 9: 99-104 [Abstract] [Full Text]  
• Seixas, S., Suriano, G., Carvalho, F., Seruca, R., Rocha, J., Di Rienzo, A. (2007). Sequence Diversity at the Proximal 14q32.1 SERPIN Subcluster: Evidence for Natural Selection Favoring the Pseudogenization of SERPINA2. Mol Biol Evol 24: 587-598 [Abstract] [Full Text]  
• Stolk, J (2006). Alpha-1-antitrypsin augmentation treatment: does one size fit all?. Thorax 61: 1034-1034 [Full Text]  
• Snyder, M. R., Katzmann, J. A., Butz, M. L., Yang, P., Dawson, D. B., Halling, K. C., Highsmith, W. E., Thibodeau, S. N. (2006). Diagnosis of {alpha}-1-Antitrypsin Deficiency: An Algorithm of Quantification, Genotyping, and Phenotyping. Clin. Chem. 52: 2236-2242 [Abstract] [Full Text]  
• Petrache, I., Fijalkowska, I., Medler, T. R., Skirball, J., Cruz, P., Zhen, L., Petrache, H. I., Flotte, T. R., Tuder, R. M. (2006). {alpha}-1 Antitrypsin Inhibits Caspase-3 Activity, Preventing Lung Endothelial Cell Apoptosis. Am. J. Pathol. 169: 1155-1166 [Abstract] [Full Text]  
• Lomas, D. A. (2006). Parker B. Francis Lectureship. Antitrypsin Deficiency, the Serpinopathies, and Chronic Obstructive Pulmonary Disease. Proc Am Thorac Soc 3: 499-501 [Abstract] [Full Text]  
• Hernandez-Espinosa, D., Minano, A., Martinez, C., Perez-Ceballos, E., Heras, I., Fuster, J. L., Vicente, V., Corral, J. (2006). L-Asparaginase-Induced Antithrombin Type I Deficiency: Implications for Conformational Diseases. Am. J. Pathol. 169: 142-153 [Abstract] [Full Text]  
• Corral, J., Gonzalez-Conejero, R., Soria, J. M., Gonzalez-Porras, J. R., Perez-Ceballos, E., Lecumberri, R., Roldan, V., Souto, J. C., Minano, A., Hernandez-Espinosa, D., Alberca, I., Fontcuberta, J., Vicente, V. (2006). A nonsense polymorphism in the protein Z-dependent protease inhibitor increases the risk for venous thrombosis. Blood 108: 177-183 [Abstract] [Full Text]  
• Persson, C., Subramaniyam, D., Stevens, T., Janciauskiene, S. (2006). Do Native and Polymeric α1-Antitrypsin Activate Human Neutrophils In Vitro?. Chest 129: 1683-1692 [Abstract] [Full Text]  
• Mazereeuw-Hautier, J., Cope, J., Ong, C., Green, A., Hovnanian, A., Harper, J. I. (2006). Topical recombinant alpha1-antitrypsin: a potential treatment for netherton syndrome?. Arch Dermatol 142: 396-398 [Full Text]  
• van Pel, M., van Os, R., Velders, G. A., Hagoort, H., Heegaard, P. M. H., Lindley, I. J. D., Willemze, R., Fibbe, W. E. (2006). Serpina1 is a potent inhibitor of IL-8-induced hematopoietic stem cell mobilization. Proc. Natl. Acad. Sci. USA 103: 1469-1474 [Abstract] [Full Text]  
• Thomsen, B., Horn, P., Panitz, F., Bendixen, E., Petersen, A. H., Holm, L.-E., Nielsen, V. H., Agerholm, J. S., Arnbjerg, J., Bendixen, C. (2006). A missense mutation in the bovine SLC35A3 gene, encoding a UDP-N-acetylglucosamine transporter, causes complex vertebral malformation. Genome Res 16: 97-105 [Abstract] [Full Text]  
• Onda, M., Belorgey, D., Sharp, L. K., Lomas, D. A. (2005). Latent S49P Neuroserpin Forms Polymers in the Dementia Familial Encephalopathy with Neuroserpin Inclusion Bodies. J. Biol. Chem. 280: 13735-13741 [Abstract] [Full Text]  
• Fulton, K. F., Buckle, A. M., Cabrita, L. D., Irving, J. A., Butcher, R. E., Smith, I., Reeve, S., Lesk, A. M., Bottomley, S. P., Rossjohn, J., Whisstock, J. C. (2005). The High Resolution Crystal Structure of a Native Thermostable Serpin Reveals the Complex Mechanism Underpinning the Stressed to Relaxed Transition. J. Biol. Chem. 280: 8435-8442 [Abstract] [Full Text]  
• Ferrarotti, I, Baccheschi, J, Zorzetto, M, Tinelli, C, Corda, L, Balbi, B, Campo, I, Pozzi, E, Faa, G, Coni, P, Massi, G, Stella, G, Luisetti, M (2005). Prevalence and phenotype of subjects carrying rare variants in the Italian registry for alpha1-antitrypsin deficiency. J. Med. Genet. 42: 282-287 [Full Text]  
• Barnes, P. J. (2004). Mediators of Chronic Obstructive Pulmonary Disease. Pharmacol. Rev. 56: 515-548 [Abstract] [Full Text]  
• Gershagen, S., Janciauskiene, S. (2004). ELISA for Specific Detection of PiZ-Related {alpha}1-Antitrypsin Deficiency. Clin. Chem. 50: 2407-2410 [Full Text]  
• Sandhaus, R A (2004). {alpha}1-Antitrypsin deficiency {middle dot} 6: New and emerging treatments for {alpha}1-antitrypsin deficiency. Thorax 59: 904-909 [Abstract] [Full Text]  
• Corral, J., Aznar, J., Gonzalez-Conejero, R., Villa, P., Minano, A., Vaya, A., Carrell, R. W., Huntington, J. A., Vicente, V. (2004). Homozygous Deficiency of Heparin Cofactor II: Relevance of P17 Glutamate Residue in Serpins, Relationship With Conformational Diseases, and Role in Thrombosis. Circulation 110: 1303-1307 [Abstract] [Full Text]  
• Miranda, E., Romisch, K., Lomas, D. A. (2004). Mutants of Neuroserpin That Cause Dementia Accumulate as Polymers within the Endoplasmic Reticulum. J. Biol. Chem. 279: 28283-28291 [Abstract] [Full Text]  
• Lomas, D A, Parfrey, H (2004). {alpha}1-Antitrypsin deficiency * 4: Molecular pathophysiology. Thorax 59: 529-535 [Abstract] [Full Text]  
• Wewers, M. D. (2004). {alpha}1-Antitrypsin Deficiency: More Than a Protease Imbalance?. Chest 125: 1607-1609 [Full Text]  
• Luisetti, M, Seersholm, N (2004). {alpha}1-Antitrypsin deficiency {middle dot} 1: Epidemiology of {alpha}1-antitrypsin deficiency. Thorax 59: 164-169 [Abstract] [Full Text]  
• Mulugeta, S., Beers, M. F. (2003). Processing of Surfactant Protein C Requires a Type II Transmembrane Topology Directed by Juxtamembrane Positively Charged Residues. J. Biol. Chem. 278: 47979-47986 [Abstract] [Full Text]  
• Barnes, P.J., Shapiro, S.D., Pauwels, R.A. (2003). Chronic obstructive pulmonary disease: molecular and cellularmechanisms. Eur Respir J 22: 672-688 [Abstract] [Full Text]  
• (2003). American Thoracic Society/European Respiratory Society Statement: Standards for the Diagnosis and Management of Individuals with Alpha-1 Antitrypsin Deficiency. Am. J. Respir. Crit. Care Med. 168: 818-900 [Full Text]  
• Honaramooz, A., Behboodi, E., Megee, S. O., Overton, S. A., Galantino-Homer, H., Echelard, Y., Dobrinski, I. (2003). Fertility and Germline Transmission of Donor Haplotype Following Germ Cell Transplantation in Immunocompetent Goats. Biol. Reprod. 69: 1260-1264 [Abstract] [Full Text]  
• Parfrey, H., Mahadeva, R., Ravenhill, N. A., Zhou, A., Dafforn, T. R., Foreman, R. C., Lomas, D. A. (2003). Targeting a Surface Cavity of {alpha}1-Antitrypsin to Prevent Conformational Disease. J. Biol. Chem. 278: 33060-33066 [Abstract] [Full Text]  
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• Picard, V., Dautzenberg, M.-D., Villoutreix, B. O., Orliaguet, G., Alhenc-Gelas, M., Aiach, M. (2003). Antithrombin Phe229Leu: a new homozygous variant leading to spontaneous antithrombin polymerization in vivo associated with severe childhood thrombosis. Blood 102: 919-925 [Abstract] [Full Text]  
• Esposito, G., Garcia, J., Mangione, P., Giorgetti, S., Corazza, A., Viglino, P., Chiti, F., Andreola, A., Dumy, P., Booth, D., Hawkins, P. N., Bellotti, V. (2003). Structural and Folding Dynamic Properties of the T70N Variant of Human Lysozyme. J. Biol. Chem. 278: 25910-25918 [Abstract] [Full Text]  
• Ferenci, P (2003). How to identify the genetic basis of gastrointestinal and liver diseases?. Gut 52: ii6-9 [Abstract] [Full Text]  
• Zhou, A., Stein, P. E., Huntington, J. A., Carrell, R. W. (2003). Serpin Polymerization Is Prevented by a Hydrogen Bond Network That Is Centered on His-334 and Stabilized by Glycerol. J. Biol. Chem. 278: 15116-15122 [Abstract] [Full Text]  
• Green, C., Brown, G., Dafforn, T. R., Reichhart, J.-M., Morley, T., Lomas, D. A., Gubb, D. (2003). Drosophila necrotic mutations mirror disease-associated variants of human serpins. Development 130: 1473-1478 [Abstract] [Full Text]  
• Wang, W.-J., Mulugeta, S., Russo, S. J., Beers, M. F. (2003). Deletion of exon 4 from human surfactant protein C results in aggresome formation and generation of a dominant negative. J. Cell Sci. 116: 683-692 [Abstract] [Full Text]  
• Robertson, A. S., Belorgey, D., Lilley, K. S., Lomas, D. A., Gubb, D., Dafforn, T. R. (2003). Characterization of the Necrotic Protein That Regulates the Toll-mediated Immune Response in Drosophila. J. Biol. Chem. 278: 6175-6180 [Abstract] [Full Text]  
• Andolfatto, S., Namour, F., Garnier, A-L., Chabot, F., Gueant, J-L., Aimone-Gastin, I. (2003). Genomic DNA extraction from small amounts of serum to be used for {alpha}1-antitrypsin genotype analysis. Eur Respir J 21: 215-219 [Abstract] [Full Text]  
• Mor, F., Quintana, F., Mimran, A., Cohen, I. R. (2003). Autoimmune Encephalomyelitis and Uveitis Induced by T Cell Immunity to Self {beta}-Synuclein. J. Immunol. 170: 628-634 [Abstract] [Full Text]  
• Lindstrom, F D, Skogh, T, Lundstrom, I M C (2002). {alpha}1 Antitrypsin deficiency in a patient with systemic vasculitis and primary Sjogren's syndrome. Ann Rheum Dis 61: 945-946 [Full Text]  
• Kosugi, S., Okamoto, H., Tamada, A., Sanchez-Franco, F. (2002). A Novel Peculiar Mutation in the Sodium/Iodide Symporter Gene in Spanish Siblings with Iodide Transport Defect. J. Clin. Endocrinol. Metab. 87: 3830-3836 [Abstract] [Full Text]  
• Cabral, C. M., Liu, Y., Moremen, K. W., Sifers, R. N. (2002). Organizational Diversity among Distinct Glycoprotein Endoplasmic Reticulum-associated Degradation Programs. Mol. Biol. Cell 13: 2639-2650 [Abstract] [Full Text]  
• Janciauskiene, S., Dominaitiene, R., Sternby, N. H., Piitulainen, E., Eriksson, S. (2002). Detection of Circulating and Endothelial Cell Polymers of Z and Wild Type alpha 1-Antitrypsin by a Monoclonal Antibody. J. Biol. Chem. 277: 26540-26546 [Abstract] [Full Text]  
• Wang, W.-J., Russo, S. J., Mulugeta, S., Beers, M. F. (2002). Biosynthesis of Surfactant Protein C (SP-C). SORTING OF SP-C PROPROTEIN INVOLVES HOMOMERIC ASSOCIATION VIA A SIGNAL ANCHOR DOMAIN. J. Biol. Chem. 277: 19929-19937 [Abstract] [Full Text]  
• Belorgey, D., Crowther, D. C., Mahadeva, R., Lomas, D. A. (2002). Mutant Neuroserpin (S49P) That Causes Familial Encephalopathy with Neuroserpin Inclusion Bodies Is a Poor Proteinase Inhibitor and Readily Forms Polymers in Vitro. J. Biol. Chem. 277: 17367-17373 [Abstract] [Full Text]