Mast cell involvement in normal human skin wound healing: expression of monocyte chemoattractant protein-1 is correlated with recruitment of mast cells which synthesize interleukin-4in vivo

Trautmann, Axel; Toksoy, Atiye; Engelhardt, Eva; Bröcker, Eva‐B.; Gillitzer, R.

doi:10.1002/(sici)1096-9896(200001)190:1<100::aid-path496>3.0.co;2-q

Cited by 179 publications

(128 citation statements)

References 33 publications

(48 reference statements)

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“…Neutralization of the CXC chemokine MIP-2 has been shown to ameliorate bleomycin-induced fibrosis (58). Lastly, the fact that MCP-1 has been shown to induce/contribute to the expression of IL-4 (32,59,60) could suggest that in the absence of CCR2 signaling, the balance in T1/T2 cytokines is skewed to favor the production of the anti-fibrotic T1 cytokines such as IFN-␥.…”

Section: Ccr2 ϫ/ϫ Mice Are Protected From Pulmonary Fibrosismentioning

confidence: 99%

Protection from Pulmonary Fibrosis in the Absence of CCR2 Signaling

Moore

Paine

Christensen

et al. 2001

The Journal of Immunology

337

292

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Pulmonary fibrosis can be modeled in animals by intratracheal instillation of FITC, which results in acute lung injury, inflammation, and extracellular matrix deposition. We have previously shown that despite chronic inflammation, this model of pulmonary fibrosis is lymphocyte independent. The CC chemokine monocyte-chemoattractant protein-1 is induced following FITC deposition. Therefore, we have investigated the contribution of the main monocyte-chemoattractant protein-1 chemokine receptor, CCR2, to the fibrotic disease process. We demonstrate that CCR2−/− mice are protected from fibrosis in both the FITC and bleomycin pulmonary fibrosis models. The protection is specific for the absence of CCR2, as CCR5−/− mice are not protected. The protection is not explained by differences in acute lung injury, or the magnitude or composition of inflammatory cells. FITC-treated CCR2−/− mice display differential patterns of cellular activation as evidenced by the altered production of cytokines and growth factors following FITC inoculation compared with wild-type controls. CCR2−/− mice have increased levels of GM-CSF and reduced levels of TNF-α compared with FITC-treated CCR2+/+ mice. Thus, CCR2 signaling promotes a profibrotic cytokine cascade following FITC administration.

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Section: Ccr2 ϫ/ϫ Mice Are Protected From Pulmonary Fibrosismentioning

confidence: 99%

Protection from Pulmonary Fibrosis in the Absence of CCR2 Signaling

Moore

Paine

Christensen

et al. 2001

The Journal of Immunology

337

292

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“…Indeed, MCs have, in addition to their well established role in immediate hypersensitivity (24), been strongly implicated in various processes in which MMP activity is involved, e.g. angiogenesis (25), wound healing (26), arthritis (27), and tumor metastasis (28), but their mechanism of action under these circumstances has not been clarified. The aim of the present investigation was therefore to address the relative importance of MCs and the MC proteases, in particular chymase, in the activation of pro-MMP-2 and -9 in vivo.…”

mentioning

confidence: 99%

A Key Role for Mast Cell Chymase in the Activation of Pro-matrix Metalloprotease-9 and Pro-matrix Metalloprotease-2

Tchougounova

Lundequist

Fajardo

et al. 2005

Journal of Biological Chemistry

287

251

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Chymases, serine proteases exclusively expressed by mast cells, have been implicated in various pathological conditions. However, the basis for these activities is not known, i.e. the in vivo substrate(s) for mast cell chymase has not been identified. In this study we show that mice lacking the chymase mouse mast cell protease 4 (mMCP-4) fail to process pro-matrix metalloprotease 9 (pro-MMP-9) to its active form in vivo, whereas both the pro and active form of MMP-9 was found in tissues of wild type mice. Moreover, the processing of pro-MMP-2 into active enzyme was markedly defective in mMCP-4 null animals. Histological analysis revealed an increase in collagen in the ear tissue of mMCP-4-deficient animals accompanied by increased ear thickness and a higher content of hydroxyproline. Furthermore, both lung and ear tissue from the knock-out animals showed a markedly increased staining for fibronectin. MMP-9 and MMP-2 are known to have a range of important activities, but the mechanisms for their activation in vivo have not been clarified previously. The present study thus indicates a key role for mast cell chymase in the regulation of pro-MMP-2 and -9 activities. Moreover, the results suggest an important role for mast cell chymase in regulating connective tissue homeostasis. When mast cells (MCs)1 are activated, they degranulate and thereby release a panel of powerful preformed inflammatory mediators, including histamine, cytokines such as tumor necrosis factor-␣, proteoglycans, and various MC-specific proteases (1, 2). The MC proteases are divided into three main subclasses, tryptases, chymases, and carboxypeptidase A (3-5), all of which are stored in the MC granule in complex with heparin proteoglycan (6, 7). Chymases, serine proteases with chymotrypsin-like substrate specificities, have potent pro-inflammatory properties (8) and have been implicated in a variety of pathophysiological conditions, e.g. angiogenesis (9), heart failure (10), and fibrosis (11). However, it has not been possible to determine the mechanism by which chymases influences these processes, i.e. the physiological substrate(s) for chymase has not been identified.Matrix metalloproteases (MMPs) are known to be involved in a variety of physiological and pathological processes and are currently attracting a large clinical interest as potential drug targets in therapeutic intervention with various diseases (12-16). The MMPs, similar to most proteolytic enzymes, are synthesized with an N-terminal propeptide that needs to be removed to achieve proteolytic activity. Thus, the physiological processes that lead to propeptide cleavage are imperative in terms of regulating the activity of most proteases (17). The MMP family currently comprises Ͼ20 members (18). The members all share common structural features but differ in regard to substrate specificities, although overlapping substrate specificities between certain members of the MMP family occur. Thus, MMP-2 and -9 share the ability to degrade denatured collagen (gelatin) and are therefore also den...

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“…This phase of the repair process coincides with the period of chronic inflammation when collagen fibers are being deposited and angiogenesis is evident. According to Trautmann et al 24 as the healing process progresses, mast cells migrate to the site of injury, dramatically increasing in numbers.…”

Section: ■ Discussionmentioning

confidence: 99%

Arnica montana does not affect mast cell populations in experimentally induced oral ulcers in rats

Perussolo¹,

Grégio²,

Azevedo‐Alanis³

et al. 2015

Medical Express

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BACKGROUND:Studies have shown that Arnica montana shows anti-inflammatory and antioxidant activities. It has been used in traditional medicine for the treatment of several disorders. The aim of this study was to investigate the effect of Arnica montana on mast cells during the wound healing of oral ulcers. METHOD: An ulcerated lesion was chemically induced on the tongue of 75 male albino rats and, then, treated topically for seven days using saline solution (control), Arnica montana gel or tincture. The animals were killed after 2

show abstract

Mast cell involvement in normal human skin wound healing: expression of monocyte chemoattractant protein-1 is correlated with recruitment of mast cells which synthesize interleukin-4in vivo

Cited by 179 publications

References 33 publications

Protection from Pulmonary Fibrosis in the Absence of CCR2 Signaling

Protection from Pulmonary Fibrosis in the Absence of CCR2 Signaling

A Key Role for Mast Cell Chymase in the Activation of Pro-matrix Metalloprotease-9 and Pro-matrix Metalloprotease-2

Arnica montana does not affect mast cell populations in experimentally induced oral ulcers in rats

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