α-Melanocyte Stimulating Hormone Acts as a Selective Inducer of Secretory Functions in Human Mast Cells

Grützkau, Andreas; Henz, Beate M.; Kirchhof, Loreen; Luger, Thomas A.; Artuc, Metin

doi:10.1006/bbrc.2000.3764

Cited by 45 publications

(34 citation statements)

References 20 publications

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“…The functional activities of human mast cells are affected (27,28). For example, the release of histamine is altered under the influence of ␣-MSH (28,29). B cells are further target cells of ␣-MSH action (10,30).…”

Section: Discussionmentioning

confidence: 99%

α-Melanocyte-Stimulating Hormone Inhibits Allergic Airway Inflammation

Raap

Brzoska²,

Sohl

et al. 2003

The Journal of Immunology

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α-Melanocyte-stimulating hormone (α-MSH) is a neuropeptide controlling melanogenesis in pigmentary cells. In addition, its potent immunomodulatory and immunosuppressive activity has been recently described in cutaneous inflammatory disorders. Whether α-MSH is also produced in the lung and might play a role in the pathogenesis of inflammatory lung conditions, including allergic bronchial asthma, is unknown. Production and functional role of α-MSH were investigated in a murine model of allergic airway inflammation. α-MSH production was detected in bronchoalveolar lavage fluids. Although aerosol challenges stimulate α-MSH production in nonsensitized mice, this rapid and marked stimulation was absent in allergic animals. Treatment of allergic mice with α-MSH resulted in suppression of airway inflammation. These effects were mediated via IL-10 production, because IL-10 knockout mice were resistant to α-MSH treatment. This study provides evidence for a novel function of α-MSH linking neuroimmune functions in allergic airway inflammation.

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Section: Discussionmentioning

confidence: 99%

α-Melanocyte-Stimulating Hormone Inhibits Allergic Airway Inflammation

Raap

Brzoska²,

Sohl

et al. 2003

The Journal of Immunology

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“…Recently, human mast cells were also found to express MC-Rs; MC-1R expression was detectable on the RNA level in both the human mast cell line HMC-1 and skin mast cells. However, less than 10% of HMC-1 cells expressed MC-1R on the protein level and in skin mast cells MC-1R protein expression was absent [27]. …”

Section: The Skin As a Target Organ For Melanocortinsmentioning

confidence: 99%

“…This antibody stained human epidermis, hair follicles, eccrine glands and endothelial cells in situ [38]. In addition, immunostaining for MC-5R was detected in vitro by FACS analysis of HMC-1 cells and human skin mast cells [27]. …”

Section: The Skin As a Target Organ For Melanocortinsmentioning

confidence: 99%

The Role of Melanocortins in Skin Homeostasis

Böhm¹,

Luger²

2000

Horm Res Paediatr

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Melanocortins are structurally related bioactive peptides which are produced by many extra-neural tissues including the skin. All of the melanocortins (α, β, and γ-melanocyte-stimulating hormone and adrenocorticotropin) have melanotropic activity but can elicit many other effects on skin cells. On the basis of in vitro and in vivo findings melanocortins have been shown to regulate immune and inflammatory responses, hair growth, exocrine gland activity and extracellular matrix composition. These effects are mediated by melanocortin receptors among which the melanocortin-1 receptor is most ubiquitously expressed by human skin cells. Simultaneous expression of melanocortins and their receptors suggest a complex autocrine and/or paracrine regulatory network whose disruption invariably affects skin homeostasis. Expression of melanocortin receptors on various skin cell types further indicates novel pharmacological targets for the treatment of skin diseases.

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“…As a secondary goal, we hoped to identify a reliable activation marker for these cells, as established for basophils. Such a marker might also be helpful in studies of mast cell activation in general because mast cells from different donors and origins differ markedly in their responsiveness to different stimuli with respect to the release of their various prestored and newly generated mediators (12,13). As a final goal, the present investigations were to provide initial insights into the intracellular distribution of LAMPs in mast cells.…”

mentioning

confidence: 99%

“…As a final goal, the present investigations were to provide initial insights into the intracellular distribution of LAMPs in mast cells. This is all the more of interest because mast cell mediators differ widely in their chemical nature, and some of them, such as histamine, heparin, and tryptase, are released from stores within specific electron-dense mast cells granules, whereas others, such as leukotrienes and prostaglandins, are rapidly generated by enzymatic cleavage from membrane phospholipids, and other mediators, the so-called cytokines, are prestored or newly synthesised by peptide assembly in the Golgi apparatus of the cells (12)(13)(14). Coexpression of LAMPs with acidic hydrolases was investigated in these granules to distinguish a lysosomal location of LAMPs from that in other organelles (15).…”

mentioning

confidence: 99%

LAMP‐1 and LAMP‐2, but not LAMP‐3, are reliable markers for activation‐induced secretion of human mast cells

et al. 2004

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BackgroundMast cells are resident tissue cells that induce anaphylactic reactions by rapidly releasing mediators after antigen‐mediated cross‐linking of immunoglobulin E receptors. In the similarly active peripheral blood basophilic leukocyte, lysosome‐associated membrane protein 3 (LAMP‐3; CD63) has been described as an activation marker, but LAMPs have not been investigated in normal tissue mast cells.MethodsIntra‐ and extracellular expressions of LAMP‐1 (CD107a), LAMP‐2 (CD107b), and LAMP‐3 (CD63) were analysed by flow cytometry, immunocytochemistry, and functional assays in unstimulated and stimulated leukemic human mast cell line 1 (HMC‐1) and skin mast cells.ResultsOn flow cytometry, all mast cells expressed LAMP‐3 at their cell membranes, whereas LAMP‐1 and LAMP‐2 were barely detectable (HMC‐1 cells) or expressed at low levels (<10% of skin mast cells). After fixation and permeabilisation, high intracellular levels of all three LAMPs were noted in both cell types. After stimulation, a rapid translocation of intracellular LAMPs to the cell membrane, with an associated release of histamine, leukotriene C4 and prostaglandin D2, was ascertained in skin mast cells only.ConclusionThese results show that LAMP‐1 and LAMP‐2 are activation markers for normal mast cells. The lack of LAMP translocation after activation of leukemic mast cells may be related to maturation or malignancy‐associated defects of these cells. © 2004 Wiley‐Liss, Inc.

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α-Melanocyte Stimulating Hormone Acts as a Selective Inducer of Secretory Functions in Human Mast Cells

Cited by 45 publications

References 20 publications

α-Melanocyte-Stimulating Hormone Inhibits Allergic Airway Inflammation

α-Melanocyte-Stimulating Hormone Inhibits Allergic Airway Inflammation

The Role of Melanocortins in Skin Homeostasis

LAMP‐1 and LAMP‐2, but not LAMP‐3, are reliable markers for activation‐induced secretion of human mast cells

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