Mast cells and vasculature in atopic dermatitis – potential stimulus of neoangiogenesis

Groneberg, David A.; Bester, Carolin; Grützkau, Andreas; Serowka, Frauke; Fischer, Axel; Henz, Beate M.; Welker, Pia

doi:10.1111/j.1398-9995.2004.00628.x

Cited by 82 publications

(68 citation statements)

References 32 publications

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“…Tryptase is collectively believed to be involved in the immuno-pathogenesis of psoriasis; however no operative mechanism has been proposed for its role in the genesis of skin inflammation (55). In the skin inflammation, mast cells have been observed mostly in upper dermis close to basal lamina (39) and recently in stratum granulosum of the epidermis in AD (40). Thus, it is conceivable that, during inflammation, high C3 levels in skin and tryptase released from activated mast cells could lead to C3a generation.…”

Section: Discussionmentioning

confidence: 99%

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Induction of C3 and CCL2 by C3a in Keratinocytes: A Novel Autocrine Amplification Loop of Inflammatory Skin Reactions

Purwar

Wittmann

Zwirner

et al. 2006

The Journal of Immunology

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The complement fragment-3a (C3a) acts via a G protein-coupled C3aR and is of importance in allergic and inflammatory diseases. Recent studies suggest the presence of complement proteins in the epidermal compartment and synthesis of some of these proteins (C3, factor B, and factor H) by human primary keratinocytes (KCs) during inflammation. However, expression of C3aR and its role in human KCs is not elucidated thus far. In this study, we demonstrate the expression of C3aR on KCs as detected by quantitative real-time RT-PCR and flow cytometry. IFN-γ and IFN-α strongly up-regulated the surface expression of C3aR on KCs among all other cytokines tested. After up-regulation of C3aR by IFN-γ and IFN-α, we observed the induction of five genes (CCL2, CCL5, CXCL8, CXCL10, and C3) after stimulation of KCs with C3a in microarray analysis. We confirmed the induction of C3 and CCL2 at RNA and protein levels. Furthermore, incubation of C3 with skin mast cells tryptase resulted in the generation of C3 fragments with C3a activity. In conclusion, our data illustrate that epidermal KCs express functional C3aR. The increases of C3 and CCL2 synthesis by C3a and C3 activation by skin mast cell tryptase delineates a novel amplification loop of complement activation and inflammatory responses that may influence the pathogenesis of allergic/inflammatory skin diseases.

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Section: Discussionmentioning

confidence: 99%

“…In skin inflammation, mast cells have been observed mostly in upper dermis close to basal lamina and in the epidermis of AD (39,40). In a previous study, C3 cleavage by tryptase derived from pulmonary mast cells in lung inflammation was shown (41).…”

Section: Functional Analysis Of C3ar On Kcsmentioning

confidence: 98%

Induction of C3 and CCL2 by C3a in Keratinocytes: A Novel Autocrine Amplification Loop of Inflammatory Skin Reactions

Purwar

Wittmann

Zwirner

et al. 2006

The Journal of Immunology

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“…Mast cells reside in the papillary dermis and undergo migration through the basal lamina into the epidermis of AD lesions. Within the epidermis, mast cells may influence keratinocyte activation and stimulation of endothelial growth with neoangiogenesis [87].…”

Section: Atopic Dermatitismentioning

confidence: 99%

The mast cell and allergic diseases: role in pathogenesis and implications for therapy

Brown

Wilson

Metcalfe

2007

Clin Experimental Allergy

239

184

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SummaryMast cells have long been recognized for their role in the genesis of allergic inflammation; and more recently for their participation in innate and acquired immune responses. Mast cells reside within tissues including the skin and mucosal membranes, which interface with the external environment; as well as being found within vascularized tissues next to nerves, blood vessels and glandular structures. Mast cells have the capability of reacting both within minutes and over hours to specific stimuli, with local and systemic effects. Mast cells express the high affinity IgE receptor (FceRI) and upon aggregation of FceRI by allergen-specific IgE, mast cells release and generate biologically active preformed and newly synthesized mediators which are involved in many aspects of allergic inflammation. While mast cells have been well documented to be essential for acute allergic reactions, more recently the importance of mast cells in reacting through pattern recognition receptors in innate immune responses has become recognized. Moreover, as our molecular understanding of the mast cell has evolved, novel targets for modulation have been identified with promising therapeutic potential.

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“…Mast cells migrate to the upper dermis in AE (39) and in the lesional skin of AE patients have even been found in the epidermis (40), thus possibly facilitating their encounter with Malassezia spp. The concentrations encountered by mast cells in vivo can only be estimated.…”

Section: Discussionmentioning

confidence: 99%

TLR2/MyD88-Dependent and -Independent Activation of Mast Cell IgE Responses by the Skin Commensal Yeast Malassezia sympodialis

Selander

Engblom

Nilsson

et al. 2009

The Journal of Immunology

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Atopic eczema (AE) is a chronic inflammatory skin disease. Approximately 50% of adult AE patients have allergen-specific IgE reactivity to the skin commensal yeast Malassezia spp. Due to the ruptured skin barrier in AE, it is likely that Malassezia can come into contact with mast cells, which are known to be involved in AE. We therefore hypothesized that Malassezia spp. can activate mast cells. Bone marrow-derived mast cells (BMMCs) were generated from wild type, TLR2, TLR4, and MyD88 gene-deleted mice and cocultured with Malassezia sympodialis extract. We recorded that M. sympodialis induced release of cysteinyl leukotrienes in a dose-dependent manner in nonsensitized and IgE-anti-trinitrophenyl-sensitized BMMCs, respectively, with three times higher levels in the latter type of cells. IgE-sensitized BMMCs also responded by degranulation as assessed by release of β-hexosaminidase, increased MCP-1 production through a MyD88-independent pathway, and activated phosphorylation of the MAPK ERK1/2. Furthermore, M. sympodialis enhanced the degranulation of IgE receptor cross-linked wild-type BMMCs and altered the IL-6 release dose-dependently. This degranulation was independent of TLR2, TLR4, and MyD88, whereas the IL-6 production was dependent on the TLR2/MyD88 pathway and MAPK signaling. In conclusion, M. sympodialis extract can activate nonsensitized and IgE-sensitized mast cells to release inflammatory mediators, to enhance the IgE-mediated degranulation of mast cells, and to modulate MAPK activation and by signaling through the TLR2/MyD88 pathway to modify the IL-6 production of IgE receptor cross-linked mast cells. Collectively, these findings indicate that M. sympodialis can activate mast cells and might thus exacerbate the inflammatory response in AE.

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Mast cells and vasculature in atopic dermatitis – potential stimulus of neoangiogenesis

Cited by 82 publications

References 32 publications

Induction of C3 and CCL2 by C3a in Keratinocytes: A Novel Autocrine Amplification Loop of Inflammatory Skin Reactions

Induction of C3 and CCL2 by C3a in Keratinocytes: A Novel Autocrine Amplification Loop of Inflammatory Skin Reactions

The mast cell and allergic diseases: role in pathogenesis and implications for therapy

TLR2/MyD88-Dependent and -Independent Activation of Mast Cell IgE Responses by the Skin Commensal Yeast Malassezia sympodialis

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