Elastase and cathepsin

This is a 29-kDa protein that has NH 2-terminal sequence homology with elastase and cathepsin G. However, it contains glycine and not serine at the predicted catalytic site, and so lacks protease and peptidase activity. Purified azurocidin kills a range of organisms (e.g. E. coli, S.faecalis, and C. albicans) in vitro. It functions optimally at pH 5.5 and in conditions of low ionic strength. 

C5a is inactivated by the myeloperoxidase-H202 system, which oxidises a methionine residue (Met 70) on the molecule group A streptococcal endo-proteinases also abolish chemotactic activity of C5a and related compounds. Neutrophil lysosomal enzymes (e.g. elastase and cathepsin G) also destroy C5a chemotactic activity, but as these proteases are inhibited by the serum antiproteinases, a -antiproteinase and a2-macroglobulin, the physiological role of neutrophilic proteases in the inactivation of C5a is questionable. Two chemotactic factor inactivators have been found in human serum an a-globulin that specifically and irreversibly inactivates C5-derived chemotactic factors, and a / -globulin that inactivates bacterial chemotactic factors. These activities are heat labile (destroyed by treatment at 56 °C for 30 min) and are distinct from those attributable to anaphylatoxin inactivator. An apparently specific inhibitor of C5-derived chemotactic activity has also been described in human synovial fluid and peritoneal fluid. This factor (molecular mass of 40 kDa) is heat stable and acts directly on C5a. 

Powers, J. C., et al. 1977. Specificity of porcine pancreatic elastase, human leukocyte elastase and cathepsin G. Inhibition with peptide chloromethyl ketones. Biochim Biophys Acta 485 156. 

N. J. Braun, I. L Bodmer, G. D. Vlrca, G. Mete-Voa, K. Mrichler, J. G. Bieth, and EL P, SchneblL Kinetic studies on the interaction of eglin c with human leukocyte elastase and cathepsin G. Biol. Chejil Hoppe-Seyter 368 299 (1987). 

Beaufort N, Leduc D, Rousselle JC, Magdolen V, Luther T, Namane A, et al. Proteolytic regulation of the urokinase receptor/CD87 on monocytic cells by neutrophil elastase and cathepsin G. J Immunol 2004 172(l) 540-549. 

Bik inhibits the trypsin serine proteases through binding of either of its two Kunitz domains. Depending on the serine protease and the Kunitz domain involved, dissociation constants (K ) range from 0.03 to 800 pM [6, 28]. Bik fragmentation and glycation also effect strength and specificity of inhibition. For example, trypsin, chymotrypsin, kallikrein, plasmin, elastase, and cathepsin are inhibited at a A) of 0.03-3 pM, whereas Factors IXa, Xa, XIa, and Xlla are less inhibited with a A) of 15-800 pM. Protease inhibition is observed with both Kunitz domains except for Factors IXa and Xa that... 

Sulfonyl Fluorides. Sulfonyl fluorides inhibit serine proteases by reacting with the active-site serine residue. Previously we investigated the rates of inhibition of human leukocyte elastase and cathepsin G by a variety of sulfonyl fluorides and found relatively little selectivity or reactivity (38). However, we have discovered recently that the introduction of fluoroacyl groups into the sulfonyl fluoride structure gives considerable reactivity and selectivity for elastase (39). 

PMN Products - Neutral proteinases of PMN lysosomes degrade a wide variety of collective tissue substrates including elastin, proteoglycan, and collagen. Cathepsin G has been found only in PMN, and elastase from these cells has a substrate gpecificity different from that of pancreatic and macrophage elastase. In addition to their effects on connective tissue components, the neutral proteinases of PMN lysosomes also stimulate the activity of other cells involved in the inflammatory response. Both elastase and cathepsin G from human PMN stimulate the incor- poration of thymidine by human peripheral blood and splenic lymphocytes. The stimulated lymphocytes are of the B lineage, with no effect seen on T lymphocytes. 

Plant - Inhibitors derived from plant sources include the black bean or soybean inhibitors (Kunltz and Bowman-Birk types),34-57 lima bean inhibitor, 38 and chickpea inhibitor.39 These are all unusual double-headed polypeptides, with two Independent reactive sites, capable of interacting with both trypsin and chymotrypsin.60-63 They also are inhibitors of granulocyte elastase and cathepsin... 

Neutral proteinases, elastase (EC 3.4.21.11), cathepsin G, and a third serine proteinase seem to be the most important mediators of these effects. In addition to their degradative properties, it was found that PMN elastase and cathepsin G can stimulate lymphocyte B antibody formation in vitro (VI). The granules have been intensively studied for their role in the oxidative burst of the PMN this aspect is discussed in Section 4.4. 

W. Watorek, H. van Halbeek, and J. Travis. The isoforms of human neutrophil elastase and cathepsin G differ in their carbohydrate side chain structures. Biol. Chem. Hoppe-Seyler 374 385 (1993). 

P. Renesto, V. Balloy, T. Kamimura, K. Masuda, A. Imaizumi, and M. Chignard. Inhibition by recombinant SLPI and half-SLPI (Asn55-Alal07) of elastase and cathepsin G activities consequence for neutrophil-platelet cooperation. Br. J. Pharmacol. 705 1100(1993). 

U. Seemtiller, K. Meier, K. Ohlsson, H. P. Muller, and H. Fritz. Isolation and characterization of a low molecular weight inhibitor (of chymotrypsin and human granulocyte elastase and cathepsin G) from leeches. Hoppe Seyler s Z Physiol. Chem. 355 1105 (1977). 

Gardiner EE, De Luca M, McNally T, Michelson AD, Andrews RK, Bemdt MC Regulation of P-selectin binding to the neutrophil P-selectin counter-receptor P-selectin glycoprotein ligand-1 by neutrophil elastase and cathepsin G. Blood 2001 98 1440-1447. 

The cytotoxic mediators of tumor and EC killing include IL-1(3, TNF-a and IFNs [37-39], defensins [highly toxic against several types of tumor cells, 40], proteases [such as elastase and cathepsin G, particularly injurious to ECs, 41] and ROS, such as nitric oxide, hydrogen peroxide (H2O2) and hypochlorous acid (HOCl) [42],... 

Potential inhibitors of human leukocyte elastase and cathepsin G. 253... 

E.J. Campbell, C.A. Owen, The sulfate groups of chondroitin sulfate- and heparan sulfate-containing proteoglycans in neutrophil plasma membranes are novel binding sites for human leukocyte elastase and cathepsin G, J. Biol. Chem. 282 (19) (2007) 14645-14654. 

However, neutrophils also release large quantities of proteases, such as elastase and cathepsin G. These proteases are the most potent secretagogues known (39). Not only do they stimulate the output of mucus from secretory cells, but they are also capable of degrading mucous glycoproteins, particularly when the DNA and actin that accompany the mucins in purulent secretions become degraded (40). Thus the net effect of the by-products of infection on mucus s rheology is rather unpredictable. 

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