The degradation of articular collagen by neutrophil proteinases

Starkey, Phyllis M.; Barrett, Alan J.; Burleigh, Mary C.

doi:10.1016/0005-2744(77)90066-3

Cited by 183 publications

(62 citation statements)

References 47 publications

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“…The other gels are collagen and enzyme controls. These observations are in agreement with Starkey et al (15). The relative contributions of the two enzymes in our system remains to be defined.…”

supporting

confidence: 94%

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Neutral Proteases of Human Polymorphonuclear Granulocytes: Putative Mediators of Pulmonary Damage

Spitznagel¹,

Modrzakowski²,

Pryzwansky³

et al. 1980

Environmental Health Perspectives

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Tissue proteolytic enzymes are currently believed to be critical to the pathogenesis of panacinar emphysema. Polymorphonuclear leukocytes (Polys) have several enzymes including elastase and cathepsin G in their azurophil granules. They have collagenase in their specific granules. We have found that this coliagenase is doubly latent. It has the lysosomal type of latency that depends on the impermeability of the unit membrane that surrounds each specific granule. In addition it has a latency that is converted to activity by proteolytic enzymes. The cathepsin G of the azurophil granule is a potent activator of this latent coUlagenase once the coliagenase is released from its membrane dependent latency. Thus latency ofenzymes, the nature of the latency and accessibility of the latent enzymes to activating mechanisms must all be taken into account in any analysis of their contribution to pathogenesis of local lung disease. Equally important is the fact that polys are not a prominent cellular component of normal lung. Polys must be attracted to the lung by chemotactic peptides. These peptides must be released by the interaction of inflammatory stimuli, such as smoke particles, with complement components or they must be provided by other sources.The hypothesis that lung damage in panacinar emphysema is mediated by polys and their proteases is attractive and suggestive evidence supporting this is available. However, more evidence that takes into full account the cell biology of the proteases and poly turnover in the lung are needed to extend the hypothesis and to form a rational basis for therapeutic and prophylactic measures.

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supporting

confidence: 94%

“…Even if collagenase has no role, the elastase is now known to depolymerize collagen (see above). This depolymerization would be expected to weaken the collagen (15).…”

mentioning

confidence: 99%

Neutral Proteases of Human Polymorphonuclear Granulocytes: Putative Mediators of Pulmonary Damage

Spitznagel¹,

Modrzakowski²,

Pryzwansky³

et al. 1980

Environmental Health Perspectives

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“…This implicates a MMP, possibly MMP-3 (stromelysin-1) which is highly expressed in cartilage (Kevorkian et al, 2004), albeit largely in an inactive proform (Martel-Pelletier et al, 1994;Mudgett et al, 1998). Other proteinases capable of cleaving in these non-helical regions include the neutrophil serine proteases cathepsin G and neutrophil elastase (Starkey, Barrett, & Burleigh, 1977) and the cysteine protease cathepsin B (Burleigh, Barrett, & Lazarus, 1974).…”

Section: Cartilage: Chondrocyte Apoptosis and Extracellular Matrix Dementioning

confidence: 99%

The role of proteases in pathologies of the synovial joint

Jones¹,

Riley²,

Buttle³

2008

The International Journal of Biochemistry & Cell Biology

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Synovial (diarthrodial) joints are employed within the body to provide skeletal mobility and have a characteristic structure adapted to provide a smooth almost frictionless surface for articulation. Pathologies of the synovial joint are an important cause of patient morbidity and can affect each of the constituent tissues. A common feature of these pathologies is degenerative changes in the structure of the tissue which is mediated, at least in part, by proteolytic activity. Most tissues of the synovial joint are composed primarily of extracellular matrix and key pathological roles in the degeneration of this matrix are performed by metalloproteinases such as matrix metallproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS). However, other proteases such as cathepsin K are likely to play an important role, especially in bone turnover. In addition to the cleavage of structural proteins, proteolytic activities are employed to regulate the activity of other proteases, growth factors, cytokines and other inflammatory mediators. Proteases combine to form complex regulatory networks, the correct functioning of which is required for tissue homeostasis and the imbalance of which may be a feature of pathology. A precise understanding of the proteases involved in these networks is required for a true understanding of the associated pathology.

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“…c Attacks N-and C-terminal nonhelical ends (telopeptides) of the collagen molecule, but does not degrade Trype I helex (37). (20).…”

Section: Collagenasementioning

confidence: 99%

“…Their designation as "elastases" derives from their ability to cleave the peptide bonds of the native, insoluble elastin molecule (37). However, at least one prototype of this class, neutrophil elastase, is capable of degrading collagen (32,34,35) elastic fibers (37), the protein portion of proteoglycans (36) and fibronectin (33).…”

Section: Elastasementioning

confidence: 99%

Role of connective tissue proteases in the pathogenesis of chronic inflammatory lung disease.

Gadek¹,

Fells²,

Zimmerman³

et al. 1984

Environ Health Perspect

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The normal structure and function of the human lung is dependent on the maintenance of the connective tissue matrix. These structural macromolecules provide the template for normal parenchymal cell architecture on which efficient gas exchange depends. In addition, the organization and amount of this extracellular matrix accounts for much of the mechanical behavior of the lung parenchyma during the respiratory cycle. The preservation of this intricate connective tissue scaffold depends on the lung's capacity to prevent enzymatic disruption of the component matrix proteins. Specifically, the integrity of the normal connective tissue skeleton of the lung is determined by the maintenance of a balance between proteases capable of cleaving these structural elements and the specific protease inhibitors. The normal extracellular matrix is preserved when the local concentrations of protease inhibitors prohibits expression of active connective tissue proteases within the lung parenchyma. Conversely, the disruption of lung structure during the course of acute and chronic inflammatory diseases of the lung is often associated with an imbalance of protease-antiprotease activity. The consequence is the expression of unimpeded proteolytic attack on the connective tissue matrix of the lung. In this context, the nature of the pulmonary lesion and its physiologic consequences, reflect the specificity of the expressed proteases for the individual connective tissue components. Experimental evidence suggests that the differential expression of collagenase and elastase, prototypes of connective tissue proteases, may determine whether the pathologic outcome is fibrosis (e.g., idiopathic pulmonary fibrosis) or destruction (e.g., emphysema) of the alveolar structures.

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The degradation of articular collagen by neutrophil proteinases

Cited by 183 publications

References 47 publications

Neutral Proteases of Human Polymorphonuclear Granulocytes: Putative Mediators of Pulmonary Damage

Neutral Proteases of Human Polymorphonuclear Granulocytes: Putative Mediators of Pulmonary Damage

The role of proteases in pathologies of the synovial joint

Role of connective tissue proteases in the pathogenesis of chronic inflammatory lung disease.

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