Secretory Granule Proteases in Rat Mast Cells. Cloning of 10 Different Serine Proteases and a Carboxypeptidase A from Various Rat Mast Cell Populations

Lützelschwab, Claudia; Pejler, Gunnar; Aveskogh, Maria; Hellman, Lars

doi:10.1084/jem.185.1.13

Cited by 143 publications

(137 citation statements)

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“…Most studies concerning mast cells in inflammatory processes have focused on low m.w. mediators and granular proteases (36,37). The present study unraveled a novel function of mast cell glycosaminoglycans in vivo as effector molecules for the expulsion of the intestinal nematode, S. venezuelensis.…”

Section: Discussionmentioning

confidence: 91%

A Role of Mast Cell Glycosaminoglycans for the Immunological Expulsion of Intestinal Nematode, Strongyloides venezuelensis

Maruyama

Yabu

Yoshida

et al. 2000

The Journal of Immunology

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We examined effects of mast cell glycosaminoglycans on the establishment of the intestinal nematode, Strongyloides venezuelensis, in the mouse small intestine. When intestinal mastocytosis occurred, surgically implanted adult worms could not invade and establish in the intestinal mucosa. In mast cell-deficient W/Wv mice, inhibition of adult worm invasion was not evident as compared with littermate +/+ control mice. Mucosal mastocytosis and inhibition of S. venezuelensis adult worm mucosal invasion was tightly correlated. To determine effector molecules for the invasion inhibition, adult worms were implanted with various sulfated carbohydrates including mast cell glycosaminoglycans. Among sulfated carbohydrates tested, chondroitin sulfate (ChS)-A, ChS-E, heparin, and dextran sulfate inhibited invasion of adult worms into intestinal mucosa in vivo. No significant inhibition was observed with ChS-C, desulfated chondroitin, and dextran. ChS-E, heparin, and dextran sulfate inhibited adhesion of S. venezuelensis adult worms to plastic surfaces in vitro. Furthermore, binding of intestinal epithelial cells to adhesion substances of S. venezuelensis, which have been implicated in mucosal invasion, was inhibited by ChS-E, heparin, and dextran sulfate. Because adult worms of S. venezuelensis were actively moving in the intestinal mucosa, probably exiting and reentering during infection, the possible expulsion mechanism for S. venezuelensis is inhibition by mast cell glycosaminoglycans of attachment and subsequent invasion of adult worms into intestinal epithelium.

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Section: Discussionmentioning

confidence: 91%

A Role of Mast Cell Glycosaminoglycans for the Immunological Expulsion of Intestinal Nematode, Strongyloides venezuelensis

Maruyama

Yabu

Yoshida

et al. 2000

The Journal of Immunology

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“…Mast cells are resident tissue cells derived from bone marrow precursors that were first identified by Ehrlich on the basis of their numerous metachromatically staining cytoplasmic granules (Galli, 1990). They are a heterogeneous population of cells, the phenotype of which can be regulated by their micro-environment (Galli, 1990;Galli, 1997;Lutzelschwab et al, 1997;Metcalfe et al, 1997). During reperfusion mast cells undergo a process of activation, reflected in the apparent increased cell size and the intensity of NOS II labeling, followed by extensive degranulation that results in a striking "doughnut" appearance of these cells after 8 hours.…”

Section: Messina Et Almentioning

confidence: 99%

Localization of Inducible Nitric Oxide Synthase to Mast Cells During Ischemia/Reperfusion Injury of Skeletal Muscle

Messina

Knight

Dowsing

et al. 2000

Laboratory Investigation

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SUMMARY:Nitric oxide contributes to tissue necrosis after ischemia-reperfusion (IR). A biochemical and immunohistochemical study was made of the amounts and localization of both Ca ϩϩ -independent nitric oxide synthase (NOS) II and Ca ϩϩ -dependent (NOS I and NOS III) in rat skeletal muscle after ischemia and 0.5, 2, 8, 16, and 24 hours reperfusion. NOS II was not detectable in control muscle or during ischemia, was first detected after 2 hours reperfusion, increased further by 8 hours, and remained elevated at 24 hours. Both NOS II and nitrotyrosine, a marker of peroxynitrite formation, were localized exclusively to mast cells except after 24 hours reperfusion when some macrophages and neutrophils also showed positive immunoreactivity. Mast cells underwent extensive degranulation during reperfusion. NOS I was not detected in injured or control muscle. The level of NOS III, which was localized to the endothelium of blood vessels of all sizes in control muscle, decreased progressively during ischemia and reperfusion to reach undetectable levels after 16 hours reperfusion. These findings indicate that most of the nitric oxide formed during IR injury is generated by NOS II located almost exclusively in mast cells. (Lab Invest 2000, 80:423-431).

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“…rMCP-5 (initially designated as rMCP-3) is the rat ␣-chymase and the homologue to the single human chymase found so far. The rat mast cell ␤-chymases rMCP-1 and rMCP-2, expressed by connective tissue mast cells and MMC, respectively, have been extensively investigated with regard to tissue distribution, charge, heparin binding, substrate specificity, inhibitor susceptibility, and structure (7)(8)(9)(10). Recent data suggest that MMC mediators, in particular rMCP-2, directly induce physiological changes in the gastrointestinal tract, such as an increase in epithelial permeability (11).…”

mentioning

confidence: 99%

“…Five of the ten rat mast cell proteases (rMCP-1, rMCP-2, rMCP-3, rMCP-4, and rMCP-5) are considered to display chymase activity (7). rMCP-5 (initially designated as rMCP-3) is the rat ␣-chymase and the homologue to the single human chymase found so far.…”

mentioning

confidence: 99%

Rat Mast Cell Protease 4 Is a β-Chymase with Unusually Stringent Substrate Recognition Profile

Karlson

Pejler

Fröman

et al. 2002

Journal of Biological Chemistry

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Activated mast cells release a variety of potent inflammatory mediators including histamine, cytokines, proteoglycans, and serine proteases. The serine proteases belong to either the chymase (chymotrypsin-like substrate specificity) or tryptase (trypsin-like specificity) family. In this report we have investigated the substrate specificity of a recently identified mast cell protease, rat mast cell protease-4 (rMCP-4). Based on structural homology, rMCP-4 is predicted to belong to the chymase family, although rMCP-4 has previously not been characterized at the protein level. rMCP-4 was expressed with an N-terminal His tag followed by an enterokinase site substituting for the native activation peptide. The enterokinase-cleaved fusion protein was labeled by diisopropyl fluorophosphate, demonstrating that it is an active serine protease. Moreover, rMCP-4 hydrolyzed MeO-Suc-Arg-Ala-Tyr-pNA, thus verifying that this protease belongs to the chymase family. rMCP-4 bound to heparin, and the enzymatic activity toward MeO-SucArg-Ala-Tyr-pNA was strongly enhanced in the presence of heparin. Detailed analysis of the substrate specificity was performed using peptide phage display technique. After six rounds of amplification a consensus sequence, Leu-Val-Trp-Phe-Arg-Gly, was obtained. The corresponding peptide was synthesized, and rMCP-4 was shown to cleave only the Phe-Arg bond in this peptide. This demonstrates that rMCP-4 displays a striking preference for bulky/aromatic amino acid residues in both the P1 and P2 positions.Mast cells are potent inflammatory cells with well known harmful effects, e.g. during allergic reactions. However, their primary beneficial function in vivo is most likely their involvement in the expulsion of nematode parasites and in the defense against bacterial infections (1-3). Two main types of mast cells have been identified in rodents, the connective tissue mast cells, which mainly reside in connective tissue and the peritoneum, and the mucosal mast cells (MMC), 1 which reside mainly in the mucosa of the respiratory and intestinal tracts.Both types of rodent mast cells are activated by antigen cross-linking of surface-bound IgE and respond by rapidly releasing mediators stored in their granules. The inflammatory mediators include histamine, proteoglycans, prostaglandins, cytokines, and neutral proteases (4). Mast cells are a particularly rich source of serine proteases belonging to the tryptase family, the chymase family, and the recently identified mMCP-8 family. Proteases belonging to the mMCP-8 family have as yet unknown substrate specificity. The tryptase family of proteases cleaves their substrate at the C-terminal side of basic amino acids (Arg and Lys), whereas the chymase family has chymotrypsin-like substrate specificity, i.e. they cleave peptides after aromatic amino acids (Phe, Tyr, and Trp). Based on phylogenetic relationships, the chymase family can be further subdivided into two groups, the ␣-and the ␤-chymases (5). In nonrodent mammals only a single ␣-chymase can be found, whereas in...

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Secretory Granule Proteases in Rat Mast Cells. Cloning of 10 Different Serine Proteases and a Carboxypeptidase A from Various Rat Mast Cell Populations

Cited by 143 publications

References 67 publications

A Role of Mast Cell Glycosaminoglycans for the Immunological Expulsion of Intestinal Nematode, Strongyloides venezuelensis

A Role of Mast Cell Glycosaminoglycans for the Immunological Expulsion of Intestinal Nematode, Strongyloides venezuelensis

Localization of Inducible Nitric Oxide Synthase to Mast Cells During Ischemia/Reperfusion Injury of Skeletal Muscle

Rat Mast Cell Protease 4 Is a β-Chymase with Unusually Stringent Substrate Recognition Profile

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