Rat Mast Cell Protease I Alters Cell Metabolism

Chan, Ien; Tharp, Michael D.

doi:10.1111/1523-1747.ep12391797

Cited by 8 publications

(8 citation statements)

References 20 publications

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“…It remains, however, uncertain whether the tryptase-containing mast cells observed in scar tissue represent newly immigrated, immature mast cells or whether they are the remnants of partially degranulated mast cells which were present in the normal tissue already prior to injury. Using murine mast cell protease I, other workers have observed an in vitro inhibition of human skin fibroblasts, keratinocytes and of 90% confluent fibrosarcoma cells (22), and another group failed to show any effect of dog chymase on hamster lung and rat fibroblasts (17). Differences compared to our present findings are most likely due to methods of cell culture since it is known that subconfluent cells respond differently from confluent cells due to cell cycle-dependent cellular alterations, in analogy to differences reported with keloids versus normal fibroblasts in response to chymase in vivo (23).…”

Section: Discussionmentioning

confidence: 99%

“…Species differences might be another reason, particularly since mast cell chymases have been described to differ in this regard, with e.g. human mast cells expressing only the a-chymase and murine mast cells both a-and b-chymase (22). The lack of a proliferative response of human keratinocytes to the a-chymase-containing murine enzyme preparation used here is, however, unlikely to be due to species differences since murine and human skin chymase recognize the same specific amino acid sequence (22,24).…”

Section: Discussionmentioning

confidence: 99%

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Mast cell chymase and tryptase during tissue turnover: analysis on in vitro mitogenesis of fibroblasts and keratinocytes and alterations in cutaneous scars

Algermissen

Hermes

Feldmann-Boeddeker

et al. 1999

Experimental Dermatology

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In order to shed further light on the potential role of mast cells during tissue turnover, we have investigated the number of mast cells containing only tryptase and those storing both tryptase and chymase by enzyme histochemistry in normal versus healing skin. Furthermore, we have studied the in vitro effect of these enzymes on the mitogenesis of subconfluent quiescent fibroblast and HaCaT keratinocyte cultures, using flowcytometric DNA analysis. Chymase-containing mast cell numbers were markedly decreased in scars (P<0.001), whereas the overall number of tryptase-containing mast cells was not decreased, although these cells were smaller and stained more faintly in scars. Chymase (5 to 300 mU/ml) induced a marked, dose-dependent in vitro mitogenic response in 3T3 fibroblasts, whereas the effects of tryptase, at up to 60 nM, were only moderate, compared to the known fibroblast mitogens EGF, TGF-alpha, alpha-thrombin and trypsin at optimal concentrations. Coincubation of either protease with EGF or alpha-thrombin had additive effects. In contrast to fibroblasts, keratinocytes showed only minor mitogenic responses to tryptase and chymase, also in comparison to other known mitogenic stimuli, and responses to EGF and alpha-thrombin were inhibited on costimulation of cells with the proteases. These findings document for the first time a potential role of mast cell chymase in connective tissue repair, with tryptase being less active on fibroblasts, and with inhibitory effects of both mast cell proteases on keratinocytes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mast cell chymase and tryptase during tissue turnover: analysis on in vitro mitogenesis of fibroblasts and keratinocytes and alterations in cutaneous scars

Algermissen

Hermes

Feldmann-Boeddeker

et al. 1999

Experimental Dermatology

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“…Proteases can influence cell biochemistry and inflammation by either proteolysis or acting as ligands that bind to specific receptors. For example, thrombin can alter cell metabolism and function as an inflammatory mediator through activation of its receptor (Chan & Tharp, 1994;Cirino et al, 1996 ). The interleukin-1B converting enzyme (ICE) activates this cytokine and can also cleave poly(ADP-ribose) polymerase (Katayama et al, 1994), an enzyme proposed to influence HD toxicity (Papirmeister et al, 1985).…”

Section: Discussionmentioning

confidence: 99%

“…The interleukin-1B converting enzyme (ICE) activates this cytokine and can also cleave poly(ADP-ribose) polymerase (Katayama et al, 1994), an enzyme proposed to influence HD toxicity (Papirmeister et al, 1985). To further complicate the situation, proteases binding to their respective receptors can enhance expression of immune receptors (Chan & Tharp, 1994;Cirino et al, 1996). Epithelial cells produce and have receptors for a myriad of immune molecules that can participate in inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

Biochemical Alterations in Rat Lung Lavage Fluid Following Acute Sulfur Mustard Inhalation: Ii. Increases in Proteolytic Activity

Clar

1997

Inhalation Toxicology

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Inhalation exposure of rats to sulfur mustard ( HD) followed by assay of lung lavage fluid with Chromozym TH ( thrombin-like) and TRY ( trypsin-like) serine protease substrates revealed a time-dependent increase in proteolytic activity. HD ( 0.35 mg) in absolute ethanol ( 100 µl) or ethanol alone ( control) was placed in a glass vapor generator at 37°C, and test rats were subjected to inhalation exposure for 50 min. Increased proteolysis of the TH substrate ( 2.6 times control levels) was seen at 4 h after HD exposure, and enhanced proteolysis of both TH and TRY substrates, 13.1 and 2.6 times control levels, respectively, was observed at 24 h. HD inhalation exposure causes lung pathology that in-53 Inhalation Toxicology, 9:53-61, 1997

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“…Mast cells possess numerous chemical mediators such as histamine, prostaglandin D 2 (PGD 2 ) , tumor necrosis factor-alpha (TNF-alpha), tryptase, and chymase (1). PGD 2 , TNF-alpha, and chymase have been reported to inhibit tumor cell growth (6,14,15).…”

Section: Discussionmentioning

confidence: 99%

Malignant Schwannoma Arising in Patients with Von Recklinghausen's Disease: Report of Two Cases and the Comparison of Mast Cells between Benign and Malignant Portions

Demitsu

Murata

Kiyosawa

et al. 1995

The Journal of Dermatology

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We described two cases of malignant schwannoma arising in patients with von Recklinghausen's disease and examined the mast cells infiltrated into histologic sections. One of the two cases histologically revealed apparent mast cell infiltration in some areas of malignant schwannoma as well as in the benign neurofibroma. The malignant lesion demonstrated significantly increased percentages of degranulated mast cells over the benign lesion using FITC-avidin staining. In an electron microscopic study, mast cells in the malignant lesion displayed empty granules, piecemeal degranulation, and canaliculi structures suggesting activation. These findings were not observed in the benign lesion. The other patient histologically showed no mast cells in the malignant lesion, although the benign neurofibroma in the patient disclosed numerous mast cells. The first patient had neither recurrence nor distant metastasis. On the other hand, the second patient without mast cells in the histology had multiple distant metastases.

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Rat Mast Cell Protease I Alters Cell Metabolism

Cited by 8 publications

References 20 publications

Mast cell chymase and tryptase during tissue turnover: analysis on in vitro mitogenesis of fibroblasts and keratinocytes and alterations in cutaneous scars

Mast cell chymase and tryptase during tissue turnover: analysis on in vitro mitogenesis of fibroblasts and keratinocytes and alterations in cutaneous scars

Biochemical Alterations in Rat Lung Lavage Fluid Following Acute Sulfur Mustard Inhalation: Ii. Increases in Proteolytic Activity

Malignant Schwannoma Arising in Patients with Von Recklinghausen's Disease: Report of Two Cases and the Comparison of Mast Cells between Benign and Malignant Portions

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