Harold A. Chapman

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Hypoxia-Inducible Factor 1α Signaling Promotes Repair of the Alveolar Epithelium after Acute Lung Injury

Jazalle McClendon, Nicole L. Jansing, Elizabeth F. Redente, Aneta Gandjeva, more

The American Journal of Pathology > 2017 > 187 > 8 > 1772-1786

During the acute respiratory distress syndrome, epithelial cells, primarily alveolar type (AT) I cells, die and slough off, resulting in enhanced permeability. ATII cells proliferate and spread onto the denuded basement membrane to reseal the barrier. Repair of the alveolar epithelium is critical for clinical recovery; however, mechanisms underlying ATII cell proliferation and spreading are not well...

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Innate Antiviral Host Defense Attenuates TGF-β Function through IRF3-Mediated Suppression of Smad Signaling

Pinglong Xu, Samantha Bailey-Bucktrout, Ying Xi, Daqi Xu, more

Molecular Cell > 2014 > 56 > 6 > 723-737

TGF-β signaling is essential in many processes, including immune surveillance, and its dysregulation controls various diseases, including cancer, fibrosis, and inflammation. Studying the innate host defense, which functions in most cell types, we found that RLR signaling represses TGF-β responses. This regulation is mediated by activated IRF3, using a dual mechanism of IRF3-directed suppression. Activated...

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Repair and Regeneration of the Respiratory System: Complexity, Plasticity, and Mechanisms of Lung Stem Cell Function

Brigid L.M. Hogan, Christina E. Barkauskas, Harold A. Chapman, Jonathan A. Epstein, more

Cell Stem Cell > 2014 > 15 > 2 > 123-138

Respiratory disease is the third leading cause of death in the industrialized world. Consequently, the trachea, lungs, and cardiopulmonary vasculature have been the focus of extensive investigations. Recent studies have provided new information about the mechanisms driving lung development and differentiation. However, there is still much to learn about the ability of the adult respiratory system...

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Activated Alveolar Epithelial Cells Initiate Fibrosis through Secretion of Mesenchymal Proteins

Jibing Yang, Sarah E. Wheeler, Miranda Velikoff, Kathryn R. Kleaveland, more

The American Journal of Pathology > 2013 > 183 > 5 > 1559-1570

Fibrosis is characterized by accumulation of activated fibroblasts and pathological deposition of fibrillar collagens. Activated fibroblasts overexpress matrix proteins and release factors that promote further recruitment of activated fibroblasts, leading to progressive fibrosis. The contribution of epithelial cells to this process remains unknown. Epithelium-directed injury may lead to activation...

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Regenerative activity of the lung after epithelial injury

Andrew E. Vaughan, Harold A. Chapman

BBA - Molecular Basis of Disease > 2013 > 1832 > 7 > 922-930

Lung epithelial cells use remarkably adaptive sensing and signaling systems to maintain a physiological state supporting gas exchange and minimizing environmental insults. One facet of epithelial adaptability is the reversible acquisition of mesenchymal features, a process termed epithelial–mesenchymal transition (EMT). Although in the adult, permanent and complete EMT appears rare or non-existent,...

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Endosomal proteases in antigen presentation

Harold A Chapman

Current Opinion in Immunology > 2006 > 18 > 1 > 78-84

Processing of cytoplasmic and endocytized foreign antigens were once thought to be completely separate pathways of peptide generation for MHC class I and class II peptide display. However, recent studies show actually that there is extensive overlap owing, in part, to the positioning of endosomal proteases at sites in which MHC class I and class II paths cross. The questions of how antigens access...

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The SERPINE2 Gene Is Associated with Chronic Obstructive Pulmonary Disease

Dawn L. DeMeo, Thomas J. Mariani, Christoph Lange, Sorachai Srisuma, more

The American Journal of Human Genetics > 2006 > 78 > 2 > 253-264

Chronic obstructive pulmonary disease (COPD) is a complex human disease likely influenced by multiple genes, cigarette smoking, and gene-by-smoking interactions, but only severe alpha 1-antitrypsin deficiency is a proven genetic risk factor for COPD. Prior linkage analyses in the Boston Early-Onset COPD Study have demonstrated significant linkage to a key intermediate phenotype of COPD on chromosome...

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Cathepsins as Transcriptional Activators?

Harold A. Chapman

Developmental Cell > 2004 > 6 > 5 > 610-611

One action of proteases is limited cleavage of latent transcription factors, releasing active factors to initiate nuclear signaling. Goulet et al., in a recent Molecular Cell paper, provide evidence that a lysosomal protease, cathepsin L, exists in a previously unsuspected isoform capable of trafficking to the nucleus and activating the CDP/Cux transcription factor. The findings should stimulate new...

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A Workshop of the Path B Study Section

Yves A. DeClerck, Arthur M. Mercurio, M. Sharon Stack, Harold A. Chapman, more

The American Journal of Pathology > 2004 > 164 > 4 > 1131-1139

The role of the extracellular matrix (ECM) in the tumor microenvironment is not limited to being a barrier against tumor invasion. The ECM is a reservoir of cell binding proteins and growth factors that affect tumor cell behavior. It is also substantially modified by proteases produced by tumor cells or stroma cells. As a result of the activity of these proteases, cell-cell and cell-ECM interactions...

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Genomewide Linkage Analysis of Quantitative Spirometric Phenotypes in Severe Early-Onset Chronic Obstructive Pulmonary Disease

Edwin K. Silverman, Lyle J. Palmer, Jonathan D. Mosley, Matthew Barth, more

The American Journal of Human Genetics > 2002 > 70 > 5 > 1229-1239

Chronic obstructive pulmonary disease (COPD) is a common, complex disease associated with substantial morbidity and mortality. COPD is defined by irreversible airflow obstruction; airflow obstruction is typically determined by reductions in quantitative spirometric indices, including forced expiratory volume at 1 s (FEV ₁ ) and the ratio of FEV ₁ to forced vital capacity (FVC). To...

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Regulation of CD1 Function and NK1.1 ⁺ T Cell Selection and Maturation by Cathepsin S

Richard J. Riese, Guo-Ping Shi, Jose Villadangos, Daniel Stetson, more

Immunity > 2001 > 15 > 6 > 909-919

NK1.1 ⁺ T cells develop and function through interactions with cell surface CD1 complexes. In I-A ^b mice lacking the invariant chain (Ii) processing enzyme, cathepsin S, NK1.1 ⁺ T cell selection and function are impaired. In vitro, thymic dendritic cells (DCs) from cathepsin S ^- ^/ ^- mice exhibit defective presentation of the CD1-restricted antigen, α-galactosylceramide...

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Cathepsins and compartmentalization in antigen presentation

Richard J Riese, Harold A Chapman

Current Opinion in Immunology > 2000 > 12 > 1 > 107-113

Intracellular trafficking and cell surface expression of MHC class II molecules is a tightly regulated process and is to a large extent, determined by the fate of the class II chaperone, the invariant chain. Inhibition of endosomal proteases critical to invariant chain proteolysis reveals marked shunting of class II complexes to lysosomal compartments. Regulation of endosomal protease activity by...

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Importance of lysosomal cysteine proteases in lung disease

Paul J Wolters, Harold A Chapman

Respiratory Research > 2000 > 1 > 3 > 1-8

The human lysosomal cysteine proteases are a family of 11 proteases whose members include cathepsins B, C, H, L, and S. The biology of these proteases was largely ignored for decades because of their lysosomal location and the belief that their function was limited to the terminal degradation of proteins. In the past 10 years, this view has changed as these proteases have been found to have specific...

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Cathepsin S Required for Normal MHC Class II Peptide Loading and Germinal Center Development

Guo-Ping Shi, Jose A. Villadangos, Glenn Dranoff, Clayton Small, more

Immunity > 1999 > 10 > 2 > 197-206

Major histocompatibility complex (MHC) class II molecules acquire antigenic peptides after degradation of the invariant chain (Ii), an MHC class II-associated protein that otherwise blocks peptide binding. Antigen- presenting cells of mice that lack the protease cathepsin S fail to process Ii beyond a 10 kDa fragment, resulting in delayed peptide loading and accumulation of cell surface MHC class...

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Endosomal proteolysis and MHC class II function

Harold A Chapman

Current Opinion in Immunology > 1998 > 10 > 1 > 93-102

Newly synthesized MHC class II α and β chains associate with a protein chaperone, the invariant chain, which promotes the proper assembly of MHC class II complexes and their trafficking through cells and prevents their untimely loading with peptides. Efficient loading of MHC class II heterodimers with antigenic peptides requires concurrent proteolytic processing of both the invariant chain and endocytosed...

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42 Beyond proteolysis: Evidence for a nonproteolytic role for uPAR in cellular migration in vivo

David A. Waltz, M. Fujita, Lisa Natkin, Harold A. Chapman

Fibrinolysis and Proteolysis > 1997 > 11 > Supplement 3 > 12

article

Plasminogen activators, integrins, and the coordinated regulation of cell adhesion and migration

Harold A Chapman

Current Opinion in Cell Biology > 1997 > 9 > 5 > 714-724

Cellular migration is critically dependent on an interplay between forces of attachment and detachment. Recent studies show that the serine protease urokinase and its major inhibitor and receptor regulate the adhesive properties of integrins, at least in part through initiation of cellular signals. These new functions for an old protease system imply intricate connections between proteolysis and adhesion...

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Structure and Chromosomal Assignment of the Human Cathepsin K Gene

Bruce D. Gelb, Guo-Ping Shi, Matthew Heller, Stanislawa Weremowicz, more

Genomics > 1997 > 41 > 2 > 258-262

Cathepsin K is a recently identified lysosomal cysteine proteinase that is the major protease responsible for bone resorption and remodeling. Mutations in this gene cause the sclerosing osteochondrodysplasia pycnodysostosis. To assess its evolutionary relatedness to other cysteine proteases and to facilitate mutation identification in patients with pycnodysostosis, a genomic clone, 74e16, containing...

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Essential Role for Cathepsin S in MHC Class II-Associated Invariant Chain Processing and Peptide Loading

]Richard J. Riese, Paula R. Wolf, Dieter Brömme, Lisa R. Natkin, more

Immunity > 1996 > 4 > 4 > 357-366

Destruction of li by proteolysis is required for MHC class II molecules to bind antigenic peptides, and for transport of the resulting complexes to the cell surface. The cysteine protease cathepsin S is highly expressed in spleen, lymphocytes, monocytes, and other class II-positive cells, and is inducible with interferon-γ. Specific inhibition of cathepsin S in B lymphoblastoid cells prevented complete...

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Molecular cloning of human cathepsin O, a novel endoproteinase and homologue of rabbit OC2

Guo-Ping Shi, Harold A. Chapman, Srirama M. Bhairi, Carrie DeLeeuw, more

FEBS Letters > 1995 > 357 > 2-3 > 129-134

A 1670-bp cDNA coding for a novel human cysteine protease has been isolated from a monocyte-derived macrophage cDNA library. This cDNA predicts a 329-amino acid preprocathepsin with more than 50% identity to both human cathepsin S and cathepsin L and 94% identity to a rabbit cDNA, termed OC2, recently isolated from osteoclasts. Based on its high homology to OC2, we have named the human enzyme cathepsin...

INFONA - science communication portal

Search results for: Harold A. Chapman

Hypoxia-Inducible Factor 1α Signaling Promotes Repair of the Alveolar Epithelium after Acute Lung Injury

Innate Antiviral Host Defense Attenuates TGF-β Function through IRF3-Mediated Suppression of Smad Signaling

Repair and Regeneration of the Respiratory System: Complexity, Plasticity, and Mechanisms of Lung Stem Cell Function

Activated Alveolar Epithelial Cells Initiate Fibrosis through Secretion of Mesenchymal Proteins

Regenerative activity of the lung after epithelial injury

Endosomal proteases in antigen presentation

The SERPINE2 Gene Is Associated with Chronic Obstructive Pulmonary Disease

Cathepsins as Transcriptional Activators?

A Workshop of the Path B Study Section

Genomewide Linkage Analysis of Quantitative Spirometric Phenotypes in Severe Early-Onset Chronic Obstructive Pulmonary Disease

Regulation of CD1 Function and NK1.1 ⁺ T Cell Selection and Maturation by Cathepsin S

Cathepsins and compartmentalization in antigen presentation

Importance of lysosomal cysteine proteases in lung disease

Cathepsin S Required for Normal MHC Class II Peptide Loading and Germinal Center Development

Endosomal proteolysis and MHC class II function

42 Beyond proteolysis: Evidence for a nonproteolytic role for uPAR in cellular migration in vivo

Plasminogen activators, integrins, and the coordinated regulation of cell adhesion and migration

Structure and Chromosomal Assignment of the Human Cathepsin K Gene

Essential Role for Cathepsin S in MHC Class II-Associated Invariant Chain Processing and Peptide Loading

Molecular cloning of human cathepsin O, a novel endoproteinase and homologue of rabbit OC2

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