scholarly journals Azurocidin -- inactive serine proteinase homolog acting as a multifunctional inflammatory mediator.

2003 ◽  
Vol 50 (3) ◽  
pp. 743-752 ◽  
Author(s):  
Wiesław Watorek
Keyword(s):  
Inflammatory Mediator ◽  
Serine Proteinase ◽  
Peptide Bond ◽  
Catalytic Triad ◽  
Antimicrobial Protein ◽  
Gram Negative Bacteria ◽  
Serine Proteinases ◽  
Heparin Binding ◽  
Heparin Binding Protein ◽  
Cleave Peptide Bond

Azurocidin, also known as cationic antimicrobial protein 37 kDa (CAP37) or heparin-binding protein (HBP) is an inactive homolog of serine proteinases residing in granulocytes. The ability to cleave peptide bond was lost due to replacement of two of the three residues from the conserved catalytic triad characteristic for serine proteinases. Azurocidin has a broad spectrum of antimicrobial activity, mainly against Gram-negative bacteria. It is also recognized as a multifunctional inflammatory mediator for its contracting effects on endothelial cells causing an increase of vascular permeability, capacity to bind endotoxin and ability to attract monocytes to inflammation sites.

scholarly journals Inactivation of papain by antithrombin due to autolytic digestion: a model of serpin inactivation of cysteine proteinases

1998 ◽  
Vol 335 (3) ◽  
pp. 701-709 ◽  
Author(s):  
Ingemar BJÖRK ◽  
Kerstin NORDLING ◽  
Elke RAUB-SEGALL ◽  
Ulf HELLMAN ◽  
Steven T. OLSON
Keyword(s):  
Cysteine Proteinase ◽  
Cathepsin L ◽  
Serine Proteinase ◽  
Peptide Bond ◽  
Enzyme Inactivation ◽  
Serine Proteinases ◽  
Cysteine Proteinases ◽  
Sds Page ◽  
Reaction Proceeds ◽  
Proteinase Inhibition

Cross-class inhibition of cysteine proteinases by serpins differs from serpin inhibition of serine proteinases primarily in that no stable serpin–cysteine proteinase complex can be demonstrated. This difference in reaction mechanism was elucidated by studies of the inactivation of the cysteine proteinases, papain and cathepsin L, by the serpin antithrombin. The two proteinases were inactivated with second-order rate constants of (1.6±0.1)×103 and (8.6±0.4)×102 M-1·s-1 respectively. An antithrombin to papain inactivation stoichiometry of ∼ 3 indicated extensive cleavage of the inhibitor concurrent with enzyme inactivation, a behaviour verified by SDS/PAGE. N-terminal sequence analyses showed cleavage predominantly at the P2–P1 bond, but also at the P2´–P3´ bond of antithrombin. The papain band in SDS/PAGE progressively disappeared on reaction of the enzyme with increasing amounts of antithrombin, but no band representing a stable antithrombin–papain complex appeared. SDS/PAGE with 125I-labelled papain showed that the disappearance of papain was caused by cleavage of the enzyme into small fragments. These results suggest a mechanism in which papain attacks a peptide bond in the reactive-bond loop of antithrombin adjacent to that involved in serine proteinase inhibition. The reaction proceeds, similarly to that between serpins and serine proteinases, to form an inactive acyl-intermediate complex, although with the substrate pathway dominating in the papain reaction. In this complex, papain is highly susceptible to proteolysis and is degraded by still active papain, which greatly decreases the lifetime of the complex and results in liberation of fragmented, inactive enzyme. This model may have relevance also for the inactivation of physiologically or pathologically important cysteine proteinases by serpins.

scholarly journals Early prolonged neutrophil activation in critically ill patients with sepsis

2021 ◽  
Vol 27 (2) ◽  
pp. 192-200
Author(s):  
Sanna Törnblom ◽  
Sara Nisula ◽  
Suvi T Vaara ◽  
Meri Poukkanen ◽  
Sture Andersson ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Intensive Care Unit Admission ◽  
Plasma Concentrations ◽  
Neutrophil Activation ◽  
Early Event ◽  
Heparin Binding ◽  
Activation Markers ◽  
Heparin Binding Protein ◽  
Pro Inflammatory Cytokines

We hypothesised that plasma concentrations of biomarkers of neutrophil activation and pro-inflammatory cytokines differ according to the phase of rapidly evolving sepsis. In an observational study, we measured heparin-binding protein (HBP), myeloperoxidase (MPO), IL-6 and IL-8 in 167 sepsis patients on intensive care unit admission. We prospectively used the emergence of the first sepsis-associated organ dysfunction (OD) as a surrogate for the sepsis phase. Fifty-five patients (of 167, 33%) developed the first OD > 1 h before, 74 (44%) within ± 1 h, and 38 (23%) > 1 h after intensive care unit admission. HBP and MPO were elevated at a median of 12 h before the first OD, remained high up to 24 h, and were not associated with sepsis phase. IL-6 and IL-8 rose and declined rapidly close to OD emergence. Elevation of neutrophil activation markers HBP and MPO was an early event in the evolution of sepsis, lasting beyond the subsidence of the pro-inflammatory cytokine reaction. Thus, as sepsis biomarkers, HBP and MPO were not as prone as IL-6 and IL-8 to the effect of sample timing.

The heparin-binding protein interactome in pancreatic diseases

Pancreatology ◽  
2013 ◽  
Vol 13 (6) ◽  
pp. 598-604 ◽  
Author(s):  
Q.M. Nunes ◽  
V. Mournetas ◽  
B. Lane ◽  
R. Sutton ◽  
D.G. Fernig ◽  
...  
Keyword(s):  
Binding Protein ◽  
Heparin Binding ◽  
Pancreatic Diseases ◽  
Heparin Binding Protein ◽  
Protein Interactome

Heparin-binding protein (HBP/CAP37): A missing link in neutrophil-evoked alteration of vascular permeability

2001 ◽  
Vol 7 (10) ◽  
pp. 1123-1127 ◽  
Author(s):  
Narinder Gautam ◽  
A. Maria Olofsson ◽  
Heiko Herwald ◽  
Lars F. Iversen ◽  
Evy Lundgren-Åkerlund ◽  
...  
Keyword(s):  
Vascular Permeability ◽  
Binding Protein ◽  
Heparin Binding ◽  
Missing Link ◽  
Heparin Binding Protein

scholarly journals Mouse macrophage elastase. Purification and characterization as a metalloproteinase

1981 ◽  
Vol 193 (2) ◽  
pp. 589-605 ◽  
Author(s):  
M J Banda ◽  
Z Werb
Keyword(s):  
Culture Medium ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Serine Proteinase ◽  
Peritoneal Macrophages ◽  
Serine Proteinases ◽  
Endogenous Inhibitor ◽  
Purification And Characterization ◽  
Predominant Form ◽  
Mouse Peritoneal Macrophages

Macrophage elastase was purified from tissue-culture medium conditioned by inflammatory mouse peritoneal macrophages. Characterized as a secreted neutral metalloproteinase, this enzyme was shown to be catalytically and immunochemically distinct from the mouse pancreatic and mouse granulocyte elastases, both of which are serine proteinases. Inhibition profiles, production of nascent N-terminal leucine residues and sodium dodecyl sulphate/polyacrylamide-gel electrophoresis of degraded elastin indicated that macrophage elastase is an endopeptidase, with properties of a metalloproteinase, rather than a serine proteinase. Macrophage elastase was inhibited by alpha 2-macroglobulin, but not by alpha 1-proteinase inhibitor. Macrophage elastase was resolved into three chromatographically distinct forms. The predominant form had mol.wt. 22 000 and was purified 4100-fold. Purification of biosynthetically radiolabelled elastase indicated that this form represented less than 0.5% of the secreted protein of macrophages. Approx. 800% of the starting activity was recovered after purification. Evidence was obtained for an excess of an endogenous inhibitor masking more than 80% of the secreted activity.

Human C21orf63 is a Heparin-binding Protein

2009 ◽  
Vol 146 (3) ◽  
pp. 369-373 ◽  
Author(s):  
Kanae Mitsunaga ◽  
Jun Harada-Itadani ◽  
Toshihide Shikanai ◽  
Hiroaki Tateno ◽  
Yuzuru Ikehara ◽  
...  
Keyword(s):  
Binding Protein ◽  
Heparin Binding ◽  
Heparin Binding Protein

scholarly journals Macrophages secrete a novel heparin-binding protein with inflammatory and neutrophil chemokinetic properties.

1988 ◽  
Vol 167 (2) ◽  
pp. 570-581 ◽  
Author(s):  
S D Wolpe ◽  
G Davatelis ◽  
B Sherry ◽  
B Beutler ◽  
D G Hesse ◽  
...  
Keyword(s):  
Sequence Data ◽  
Gel Filtration ◽  
Tumor Cell Line ◽  
Neutrophil Infiltration ◽  
Host Responses ◽  
Polymorphonuclear Cells ◽  
Heparin Binding ◽  
Heparin Binding Protein ◽  
Inflammatory Protein ◽  
Sds Page

We report the identification and purification of a new inflammatory monokine synthesized by the macrophage tumor cell line RAW 264.7 in response to endotoxin. This monokine, which we term "macrophage inflammatory protein" (MIP), is a doublet with an apparent molecular mass of approximately 8,000 daltons on SDS-PAGE but forms aggregates of greater than 2 x 10(6) daltons as assessed by gel filtration. Partial NH2-terminal amino acid sequence data reveal no significant homology with any previously described protein. Although the monokine is anionic under physiological conditions, it is one of two major macrophage-secreted proteins that bind to heparin at high salt concentrations. At 100 ng/ml or greater, MIP is chemokinetic for human polymorphonuclear cells and triggers hydrogen peroxide production. Subcutaneous injection of 10 ng or greater of MIP into footpads of C3H/HeJ mice elicits an inflammatory response, characterized by neutrophil infiltration. These findings suggest that MIP is an endogenous mediator that may play a role in the host responses that occur during endotoxemia and other inflammatory events.

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