Neutral Proteinases from Human Inflammatory Cells: A Critical Review of Their Role in Extracellular Matrix Degradation

Senior, Robert M.; Campbell, Edward J.

doi:10.1016/s0272-2712(18)30954-5

Cited by 52 publications

(16 citation statements)

References 107 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, NE can cleave coagulation factors (fibrinogen and factors V, VII, XII, and XIII), plasminogen, IgG, IgA, and IgM, complement factors C3 and C5, complement receptors, and gp120, the coat protein of the human immunodeficiency virus [43][44][45]. It may also cleave other proteases found within neutrophil granules [46] and also other protease inhibitors [47,48] leading to their activation or their loss of function. (Table: 1) NE has also been shown to upregulate pro-inflammatory cytokines.…”

Section: Neutrophil Elastase Functions (Figure 3)mentioning

confidence: 99%

Targeting neutrophil elastase in cystic fibrosis

Kelly

Greene

McElvaney

2008

Expert Opinion on Therapeutic Targets

View full text Add to dashboard Cite

show abstract

Section: Neutrophil Elastase Functions (Figure 3)mentioning

confidence: 99%

Targeting neutrophil elastase in cystic fibrosis

Kelly

Greene

McElvaney

2008

Expert Opinion on Therapeutic Targets

View full text Add to dashboard Cite

show abstract

“…NE is the major protease contained within the azurophilic granules of neutrophils [108,114]. This enzyme is also found in much smaller amounts in monocytes and mast cells [115,116], although its role in these cells is not yet clear.…”

Section: Neutrophil Elastasementioning

confidence: 99%

“…However, when the protease concentration in the local milieu overwhelms the local antiprotease protective screen, such as occurs in CF patients, the result is unbridled degradation of one or more lung matrix or cellular components [108]. Whereas interaction with an antiprotease generally results in the permanent and irreversible inhibition of the protease and loss of the antiprotease's ability to function again, once a protease interacts with and degrades a natural substrate, the protease is usually free to continue to destroy other tissue components.…”

Section: Neutrophil Elastasementioning

confidence: 99%

Interleukin-1, Neutrophil Elastase, and Lipopolysaccharide: Key Pro- Inflammatory Stimuli Regulating Inflammation in Cystic Fibrosis

Carroll¹,

Greene²,

Taggart³

et al. 2005

CRMR

View full text Add to dashboard Cite

Cystic fibrosis (CF) is a common fatal genetic disease among Caucasians of European descent that is characterized by neutrophil-dominated airway inflammation due to intrinsic cellular abnormalities in the affected epithelial cells. A number of proinflammatory stimuli are responsible for aggravating inflammatory responses in CF bronchial epithelium. Two important host-derived factors with potent proinflammatory effects in CF are interleukin-1 (IL-1) and neutrophil elastase (NE). Microbial-derived factors also have importance in the CF lung, as a significant factor by which pulmonary inflammation is mediated in CF is by Pseudomonas aeruginosa infection. Pseudomonas antigens, including lipopolysaccharide (LPS), can exacerbate pulmonary inflammation in CF by exaggerating proinflammatory gene expression via Toll-like receptor (TLR) activation. TLRs belong to a family of proteins that can recognize and discriminate a diverse array of microbial antigens. Following their activation TLRs transduce intracellular signals that regulate proinflammatory gene expression. Intriguingly IL-1, NE and LPS all utilize the same intracellular signaling pathways to induce their effects. This review will summarise what is known regarding the roles of these important proinflammatory stimuli and their effects on CF epithelium and describe current and novel therapeutic strategies for the treatment of CF lung disease.

show abstract

“…Upon activation, infiltrating neutrophils secrete proteolytic enzymes known to degrade the extracellular matrix, including neutrophil elastase (NE), matrix metallopeptidase-9 (MMP-9), cathepsin G, and collagenase (Janoff, 1985; Senior and Campbell, 1983; Weiss, 1989). These proteinases, along with others such as plasmin and plasminogen activators, have been detected in BP blister fluid and within lesional/perilesional skin sites on BP patients (Gissler et al, 1992; Grando et al, 1989a; Grando et al, 1989b; Kramer and Reinartz, 1993; Oikarinen et al, 1983; Stahle-Backdahl et al, 1994; Welgus et al, 1986).…”

Section: Introductionmentioning

confidence: 99%

Neutrophil elastase cleaves the murine hemidesmosomal protein BP180/type XVII collagen and generates degradation products that modulate experimental bullous pemphigoid

et al. 2012

Self Cite

View full text Add to dashboard Cite

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease associated with autoantibodies against the hemidesmosomal proteins BP180 and BP230. In the IgG passive transfer model of BP, blister formation is triggered by anti-BP180 IgG and depends on complement activation, mast cell degranulation, and neutrophil recruitment. Mice lacking neutrophil elastase (NE) do not develop experimental BP. Here, we demonstrated that NE degrades recombinant mouse BP180 within the immunodominant extracellular domain at amino acid positions 506 and 561, generating peptide p561 and peptide p506. Peptide p561 is chemotactic for neutrophils both in vitro and in vivo. Local injection of NE into B6 mice recruits neutrophils to the skin, and neutrophil infiltration is completely blocked by co-injection with the NE inhibitor α1-proteinase inhibitor. More importantly, NE directly cleaves BP180 in mouse and human skin, as well as the native human BP180 trimer molecule. These results demonstrate that (i) NE directly damages the extracellular matrix and (ii) NE degradation of mouse BP180 generates neutrophil chemotactic peptides that amplify disease severity at the early stage of the disease.

show abstract

Neutral Proteinases from Human Inflammatory Cells: A Critical Review of Their Role in Extracellular Matrix Degradation

Cited by 52 publications

References 107 publications

Targeting neutrophil elastase in cystic fibrosis

Targeting neutrophil elastase in cystic fibrosis

Interleukin-1, Neutrophil Elastase, and Lipopolysaccharide: Key Pro- Inflammatory Stimuli Regulating Inflammation in Cystic Fibrosis

Neutrophil elastase cleaves the murine hemidesmosomal protein BP180/type XVII collagen and generates degradation products that modulate experimental bullous pemphigoid

Contact Info

Product

Resources

About