Interaction of Secretory Leukocyte Protease Inhibitor with Proteinase-3

Rao, Narayanam V.; Marshall, Bruce C.; Gray, Beulah H.; Hoidal, John R.

doi:10.1165/ajrcmb/8.6.612

Cited by 65 publications

(43 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Inhibition of leukocyte motility (which inhibited neutrophil migration into the airways) prevented chemoattractant-induced GC degranulation, implicating neutrophils and their products in the response. Neutrophils contain three proteases capable of causing secretion: elastase, cathepsin G [16] and proteinase-3 [26,27]. In the present studies, pretreatment with ICI 200,355, a selective inhibitor of elastase and proteinase-3 but not cathepsin G [28], prevented chemoattractant-induced GC degranulation.…”

Section: Discussionsupporting

confidence: 50%

Role of Neutrophil Elastase in Hypersecretion During COPD Exacerbations, and Proposed Therapies

Nadel

2000

Chest

View full text Add to dashboard Cite

Goblet cell (GC) hyperplasia and mucous plugging are common in patients with acute asthma. These patients also show neutrophil recruitment into the airways. Neutrophils contain elastase, a potent secretagogue in airways. Therefore, it was reasoned that neutrophil recruitment, by releasing elastase, could result in GC hypersecretion. When neutrophil chemoattractants were instilled in the airways of guinea-pigs, time-dependent neutrophil recruitment and GC degranulation occurred. An inhibitor of leukocyte infiltration (NP15669) prevented both responses, implicating neutrophils. An inhibitor of neutrophil elastase (ICI 200,355) abolished GC degranulation, implicating elastase. Further studies implicate movement of elastase from cytoplasmic granules to the neutrophil surface, and they suggest a role for adhesion molecules on neutrophils and on GCs in neutrophil-dependent GC degranulation. Similarly, instillation of ovalbumin (OVA) into airways of OVA-sensitized guinea-pigs caused early recruitment of neutrophils and GC degranulation. GC degranulation was prevented by pretreatment with NP15669 or ICI 200,355. These results implicate neutrophil release of elastase in allergen-induced hypersecretion. The results suggest a mechanism for the mucous plugging that occurs in acute asthma; prevention of neutrophil recruitment, prevention of neutrophil-GC adhesion, or inhibition of elastase activity could provide effective therapy for this serious pathophysiological abnormality. Eur Respir J 1999; 13: 190±196.

show abstract

Section: Discussionsupporting

confidence: 50%

Role of Neutrophil Elastase in Hypersecretion During COPD Exacerbations, and Proposed Therapies

Nadel

2000

Chest

View full text Add to dashboard Cite

show abstract

“…In this regard, whether CG and PR3 are as potent as NE to degrade TLR-4 needs to be assessed. This could be of important biological relevance given that these proteases are all released from neutrophil granules, but show different susceptibilities to inactivation by physiological protease inhibitors such as SLPI (50). Interestingly, inspection of the primary structure of TLR-4 especially within the putative extracellular domain (amino acid sequence from 26 to 638, NCBI accession number Q9QUK6) reveals the presence of peptide bonds that are preferred by the enzymes (51).…”

Section: Discussionmentioning

confidence: 99%

Neutrophil Elastase Modulates Cytokine Expression

Benabid

Wartelle

Malleret

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Neutrophil elastase (NE) is a potent serine protease with bactericidal activity against Pseudomonas aeruginosa. Results: We now provide evidence that NE modulates inflammatory cytokine expression in response to this pathogen. Conclusion: In addition to its bactericidal action, NE promotes cytokine response that contributes to host antibacterial defense. Significance: This finding reveals that NE plays a multifaceted role in protecting against bacterial infections.

show abstract

“…To discriminate between these two proteases, SLPI and AAPA-CMK were employed. Both are effective inhibitors of elastase, but do not inhibit proteinase 3 (54,55). Therefore, if proteinase 3 were responsible for degrading the DBP binding site, SLPI and AAPA-CMK should have shown no increase in binding over the untreated control.…”

Section: Discussionmentioning

confidence: 99%

Elastase Controls the Binding of the Vitamin D-Binding Protein (Gc-Globulin) to Neutrophils: A Potential Role in the Regulation of C5a Co-Chemotactic Activity

DiMartino

Shah

Trujillo

et al. 2001

The Journal of Immunology

View full text Add to dashboard Cite

The vitamin D-binding protein (DBP) binds to the plasma membranes of numerous cell types and mediates a diverse array of cellular functions. DBP bound to the surface of leukocytes serves as a co-chemotactic factor for C5a, significantly enhancing the chemotactic activity of pM concentrations of C5a. This study investigated the regulation of DBP binding to neutrophils as a possible key step in the process of chemotaxis enhancement to C5a. Using radioiodinated DBP as a probe, neutrophils released 70% of previously bound DBP into the extracellular media during a 60-min incubation at 37°C. This was suppressed by serine protease inhibitors (PMSF, Pefabloc SC), but not by metallo- or thiol-protease inhibitors. DBP shed from neutrophils had no detectable alteration in its m.w., suggesting that a serine protease probably cleaves the DBP binding site, releasing DBP in an unaltered form. Cells treated with PMSF accumulate DBP vs time with over 90% of the protein localized to the plasma membrane. Purified neutrophil plasma membranes were used to screen a panel of protease inhibitors for their ability to suppress shedding of the DBP binding site. Only inhibitors to neutrophil elastase prevented the loss of membrane DBP-binding capacity. Moreover, treatment of intact neutrophils with elastase inhibitors prevented the generation of C5a co-chemotactic activity from DBP. These results indicate that steady state binding of DBP is essential for co-chemotactic activity, and further suggest that neutrophil elastase may play a critical role in the C5a co-chemotactic mechanism.

show abstract

Interaction of Secretory Leukocyte Protease Inhibitor with Proteinase-3

Cited by 65 publications

References 36 publications

Role of Neutrophil Elastase in Hypersecretion During COPD Exacerbations, and Proposed Therapies

Role of Neutrophil Elastase in Hypersecretion During COPD Exacerbations, and Proposed Therapies

Neutrophil Elastase Modulates Cytokine Expression

Elastase Controls the Binding of the Vitamin D-Binding Protein (Gc-Globulin) to Neutrophils: A Potential Role in the Regulation of C5a Co-Chemotactic Activity

Contact Info

Product

Resources

About