Detection of MCT and MCTC types of human mast cells by immunohistochemistry using new monoclonal anti-tryptase and anti-chymase antibodies.

Irani, Anne-Marie; Bradford, Timothy R.; Kepley, Christopher L.; Schechter, Norman M.; Schwartz, Lawrence B.

doi:10.1177/37.10.2674273

Cited by 382 publications

(268 citation statements)

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“…MC TC contains both chymase and tryptase, while MC T expresses tryptase but not chymase. Because MC TC predominates in the skin (Irani et al, 1989), chymase has been implicated in the pathogenesis of skin disorders complicated by mast cell accumulation, eg, AD (DeMora et al, 1996;Tanaka et al, 1999) and scleroderma (Irani et al, 1992;Kakizoe et al, 2001).Here, we report that the inhibitor for chymase inhibits the dermatitis induced by repeated challenge with DNFB, judging by the skin thickness and eosinophil infiltration, and that purified chymase elicits skin response similar to that induced by the DNFB painting. These findings suggest that chymase may participate in the pathogenesis of AD by promoting eosinophil infiltration at the inflammation sites.…”

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confidence: 72%

Section: Discussionmentioning

confidence: 99%

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Chymase Participates in Chronic Dermatitis by Inducing Eosinophil Infiltration

Tomimori

Muto

Fukami

et al. 2002

Laboratory Investigation

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SUMMARY:An epicutaneous application of 2,4-dinitrofluorobenzene (DNFB) to a mouse ear caused a transient skin swelling, and the repetition of the challenge enlarged the contact dermatitis. The repeated challenge with DNFB also induced eosinophil infiltration on the application site. Administration of a chymase inhibitor significantly inhibited the ear swelling as well as eosinophil accumulation. An intradermal injection of human chymase to the mouse ear also elicited transient skin swelling and eosinophil infiltration, both of which were augmented in proportion to the number of injections. Human serum albumin and heat-inactivated chymase failed to induce such skin reactions, suggesting the participation of proteolytic activity of the enzyme. In addition, chymase stimulated eosinophil migration in vitro in a concentration-dependent manner. Taken together, these observations suggest that mast cell chymase may contribute to development of the DNFB-induced dermatitis, probably by promoting eosinophil infiltration. It is therefore possible that chymase plays a role in pathogenesis of chronic dermatitis such as atopic dermatitis. (Lab Invest 2002, 82:789 -794).A topic dermatitis (AD) is a chronic eczematous skin disorder characterized by dry and itchy skin. The patients with AD often have a family history of other allergic diseases including asthma and hay fever. Although AD is known to be a manifestation of immediate hypersensitivity mediated by IgE, delayed-type hypersensitivity is also involved in the skin reaction of the patients (Tanaka et al, 1994;Varela et al, 1999). Interestingly, in mice, repeated application of contact sensitizing agents, such as 2,4-dinitrofluorobenzene (DNFB) and trinitrochlorobenzene, develops an immediate-type reaction, in contrast to a single application that causes a typical delayed-type reaction (Kitagaki et al, 1995(Kitagaki et al, , 1997. Repeated elicitation with such agents not only increases the serum level of IgE but also induces Th2-type cytokine expression (Nagai et al, 1997b). In addition, mast cell accumulation occurs in the dermis because of the repeated challenge (Kitagaki et al, 1995), as is often observed in AD patients. Therefore, this animal model is thought to be valuable for studying human AD.Chymase is a chymotrypsin-like serine protease and is primarily stored in secretory granules of mast cells (Schwartz and Austen, 1980). Chymase cleaves a variety of physiological substances, including metalloproteases (Fang et al, 1997), procollagen (Kofford et al, 1997), precursor of interleukin 1␤ (IL-1␤) (Mizutani et al, 1991b), and membrane-associated stem cell factor (Longley et al, 1997), while its precise role is not clear. Human mast cells are classified into two types, MC TC and MC T , based on their composition of serine protease (Irani et al, 1986). MC TC contains both chymase and tryptase, while MC T expresses tryptase but not chymase. Because MC TC predominates in the skin (Irani et al, 1989), chymase has been implicated in the pathogenesis of skin disorders complic...

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confidence: 72%

Section: Discussionmentioning

confidence: 99%

Chymase Participates in Chronic Dermatitis by Inducing Eosinophil Infiltration

Tomimori

Muto

Fukami

et al. 2002

Laboratory Investigation

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“…It is now widely admitted that the characteristic features for the identification of human mast cells is their content on tryptase and chymase, which are the dominant protein components of their secretory granules [56,57]. In fact, only mast cells display immunoreactivity for these neutral proteases and tryptase was shown to be present in all mast cells identified by classic histochemical dyes such as highly acidic toluidine blue [58].…”

Section: Discussionmentioning

confidence: 99%

Expression of functional major histocompatility complex class II molecules on HMC-1 human mast cells

Dimitriadou

Mécheri

Koutsilieris

et al. 1998

Journal of Leukocyte Biology

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“…1 The abbreviations used are: N-proteinase, amino-terminal procollagen propeptidase; C-propeptide, carboxyl-terminal procollagen telopeptide; N-propeptide, amino-terminal procollagen telopeptide; PAGE, polyacrylamide gel electrophoresis; MC TC , tryptase-positive, chymasepositive mast cell type; C-proteinase, carboxyl-terminal procollagen propeptidase; pN-collagen, collagen intermediate following enzymatic removal of the carboxyl telopeptide region; PICP, procollagen type I carboxyl-terminal propeptide; serpins, serine protease inhibitors in the plasma.…”

Section: Purification Of Procollagen-human Intestinal Smooth Muscle Cmentioning

confidence: 99%

Cleavage of Type I Procollagen by Human Mast Cell Chymase Initiates Collagen Fibril Formation and Generates a Unique Carboxyl-terminal Propeptide

Kofford

Schwartz

Schechter

et al. 1997

Journal of Biological Chemistry

181

116

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The ability of human mast cell chymase and tryptase to process procollagen was examined. Purified human intestinal smooth muscle cell procollagen was incubated with human mast cell tryptase or human mast cell chymase. Purified chymase, but not tryptase, exhibited procollagen proteinase activity in the presence of EDTA. Addition of purified porcine heparin over a range of 0.1-100 g/ml did not affect either the rate or the products of procollagen chymase cleavage. The cleavage site of chymase on the pro-␣1(I) collagen carboxyl terminus was found to be in the propeptide region at Leu-1248-Ser-1249. Cleavage at this site suggested that the collagen products would form fibrils and confirmed the production of a unique carboxyl-terminal propeptide. Turbidometric fibril formation assay demonstrated de novo formation of chymase-generated collagen fibrils with characteristic lag, growth, and plateau phases. When observed by dark field microscopy, these fibrils were similar to fibrils formed by the action of procollagen proteinases. Thus, mast cell chymase, but not tryptase, exhibits procollagen peptidase-like activity as evidenced by its ability to process procollagen to fibrilforming collagen with concurrent formation of a unique carboxyl-terminal propeptide. These data demonstrate that mast cell chymase has a potential role in the regulation of collagen biosynthesis and in the pathogenesis of fibrosis.Mast cells are abundant in connective tissues of skin, lung, and intestine (1, 2). Increased numbers (or increased activity) of mast cells are associated with fibrotic disorders such as scleroderma, pulmonary fibrosis, and Crohn's disease (3-5). The precise role for mast cells in connective tissue biology and fibrosis is not known. One potential mechanism for mast cell involvement in these processes is through the production of unique proteolytic enzymes that may act on matrix proteins. Mast cell enzymes include the neutral proteases tryptase, chymase, cathepsin G, and a zinc-dependent carboxypeptidase (6). Although chymase and tryptase cleave fibronectin (7-9) and chymase cleaves vitronectin (10), no direct effect of these enzymes on procollagen or collagen has been demonstrated.Because procollagen (the precursor of collagen) requires proteolytic cleavage in the extracellular space prior to normal collagen fibril formation, we have speculated that newly secreted procollagen may be a substrate for mast cell proteolytic enzymes. The smooth muscle cells of the intestinal muscularis are a major contributor of collagen to the extracellular matrix in normal and fibrotic human intestine (11). Therefore, in vitro studies were performed to test the above hypothesis utilizing procollagen secreted by human intestinal smooth muscle cells. MATERIALS AND METHODSPurification of Procollagen-Human intestinal smooth muscle cells (12) were grown to confluence in Dulbecco's modified Eagle's medium containing 200 units/ml penicillin, 0.2 mg/ml streptomycin, 50 units/ml Nystatin, and 10% fetal bovine serum. Cell monolayers were then rinsed wit...

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Detection of MCT and MCTC types of human mast cells by immunohistochemistry using new monoclonal anti-tryptase and anti-chymase antibodies.

Cited by 382 publications

References 7 publications

Chymase Participates in Chronic Dermatitis by Inducing Eosinophil Infiltration

Chymase Participates in Chronic Dermatitis by Inducing Eosinophil Infiltration

Expression of functional major histocompatility complex class II molecules on HMC-1 human mast cells

Cleavage of Type I Procollagen by Human Mast Cell Chymase Initiates Collagen Fibril Formation and Generates a Unique Carboxyl-terminal Propeptide

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