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Modulation of basophil activity: a novel function of the neuropeptide ?-melanocyte-stimulating hormone

Modulation of basophil activity: a novel function of the neuropeptide ?-melanocyte-stimulating hormone
Modulation of basophil activity: a novel function of the neuropeptide ?-melanocyte-stimulating hormone
Background

Little is known about the effect of neuropeptides on basophils, which are important effector cells in immune and allergic responses.

Objective

This study aimed at revealing the role of ?-melanocyte–stimulating hormone (?-MSH) on basophil function.

Methods

Expression of melanocortin receptors and proopiomelanocortin (POMC) was analyzed by means of RT-PCR, Western immunoblotting, fluorescence-activated cell sorting, and double-immunofluorescence analysis. Signal transduction studies included cyclic AMP and Ca2+ mobilization assays. Basophil activity was assessed based on CD63 surface expression and cytokine release.

Results

MC-1R expression was detectable in basophils isolated from human peripheral blood, as well as in basophils within nasal tissue. In isolated basophils from human blood, truncated POMC transcripts were present, but there was no POMC protein. Treatment of basophils with ?-MSH increased intracellular Ca2+ but not cyclic AMP levels. ?-MSH at physiologic doses potently suppressed basophil activation induced by N-formyl-methionyl-leucyl-phenylalanine, phorbol 12-myristate 13-acetate, or grass pollen allergen in whole blood of healthy or allergic subjects, respectively. The effect of ?-MSH on basophil activation was MC-1R mediated (as shown by blockade with a peptide analogue of agouti-signaling protein) and imitated by adrenocorticotropic hormone but not elicited by the tripeptides KPV and KdPT, both of which lack the central pharmacophore of ?-MSH. Moreover, ?-MSH at physiologic doses significantly suppressed secretion of 3 proallergic cytokines, IL-4, IL-6, and IL-13, in basophils stimulated with anti-IgE, N-formyl-methionyl-leucyl-phenylalanine, or phorbol 12-myristate 13-acetate.

Conclusion

Our findings highlight a novel functional activity of ?-MSH, which acts as a natural antiallergic basophil-response modifier. These findings might point to novel therapeutic strategies in treating allergic diseases.
basophils, melanocyte-stimulating hormone, melanocortin receptors, neuropeptides
0091-6749
1085-1093
Böhm, Markus
cdfe5288-08f1-4466-a2b0-6d6bbbea555f
Apel, Mara
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Sugawara, Koji
6c70ad5a-6219-4c84-a1f9-b372c19dc6b2
Brehler, Randolf
9a1bed76-f26e-41eb-b696-6091fa57498d
Jurk, Kerstin
1e43b3ac-85f4-41eb-a1de-29100cb1d961
Luger, Thomas A.
58152471-de0a-4dce-a813-8e02da38b812
Haas, Helmut
b25965ef-23ac-46be-a4eb-fab54cc481f0
Paus, Ralf
aecd069e-f385-4cf2-9c40-908f2e8a7b68
Eiz-Vesper, Britta
69e9625e-973b-461e-962f-b9b0ca2a9548
Walls, Andrew F.
aaa7e455-0562-4b4c-94f5-ec29c74b1bfe
Ponimaskin, Evgeni
79d33120-03a3-41b4-82ce-e5e26a889d75
Gehring, Manuela
dfef6bee-fd8a-4b93-a0e2-cfd33d148695
Kapp, Alexander
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Raap, Ulrike
eb13d6a4-2b1a-4ab2-8842-a12849980f61
Böhm, Markus
cdfe5288-08f1-4466-a2b0-6d6bbbea555f
Apel, Mara
1732e808-ed24-4175-b92a-f1b9376eddad
Sugawara, Koji
6c70ad5a-6219-4c84-a1f9-b372c19dc6b2
Brehler, Randolf
9a1bed76-f26e-41eb-b696-6091fa57498d
Jurk, Kerstin
1e43b3ac-85f4-41eb-a1de-29100cb1d961
Luger, Thomas A.
58152471-de0a-4dce-a813-8e02da38b812
Haas, Helmut
b25965ef-23ac-46be-a4eb-fab54cc481f0
Paus, Ralf
aecd069e-f385-4cf2-9c40-908f2e8a7b68
Eiz-Vesper, Britta
69e9625e-973b-461e-962f-b9b0ca2a9548
Walls, Andrew F.
aaa7e455-0562-4b4c-94f5-ec29c74b1bfe
Ponimaskin, Evgeni
79d33120-03a3-41b4-82ce-e5e26a889d75
Gehring, Manuela
dfef6bee-fd8a-4b93-a0e2-cfd33d148695
Kapp, Alexander
9e731f1c-6508-4810-9b0e-f2e96cdd8cde
Raap, Ulrike
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Böhm, Markus, Apel, Mara, Sugawara, Koji, Brehler, Randolf, Jurk, Kerstin, Luger, Thomas A., Haas, Helmut, Paus, Ralf, Eiz-Vesper, Britta, Walls, Andrew F., Ponimaskin, Evgeni, Gehring, Manuela, Kapp, Alexander and Raap, Ulrike (2012) Modulation of basophil activity: a novel function of the neuropeptide ?-melanocyte-stimulating hormone. Journal of Allergy and Clinical Immunology, 129 (4), 1085-1093. (doi:10.1016/j.jaci.2011.11.012). (PMID:22178636)

Record type: Article

Abstract

Background

Little is known about the effect of neuropeptides on basophils, which are important effector cells in immune and allergic responses.

Objective

This study aimed at revealing the role of ?-melanocyte–stimulating hormone (?-MSH) on basophil function.

Methods

Expression of melanocortin receptors and proopiomelanocortin (POMC) was analyzed by means of RT-PCR, Western immunoblotting, fluorescence-activated cell sorting, and double-immunofluorescence analysis. Signal transduction studies included cyclic AMP and Ca2+ mobilization assays. Basophil activity was assessed based on CD63 surface expression and cytokine release.

Results

MC-1R expression was detectable in basophils isolated from human peripheral blood, as well as in basophils within nasal tissue. In isolated basophils from human blood, truncated POMC transcripts were present, but there was no POMC protein. Treatment of basophils with ?-MSH increased intracellular Ca2+ but not cyclic AMP levels. ?-MSH at physiologic doses potently suppressed basophil activation induced by N-formyl-methionyl-leucyl-phenylalanine, phorbol 12-myristate 13-acetate, or grass pollen allergen in whole blood of healthy or allergic subjects, respectively. The effect of ?-MSH on basophil activation was MC-1R mediated (as shown by blockade with a peptide analogue of agouti-signaling protein) and imitated by adrenocorticotropic hormone but not elicited by the tripeptides KPV and KdPT, both of which lack the central pharmacophore of ?-MSH. Moreover, ?-MSH at physiologic doses significantly suppressed secretion of 3 proallergic cytokines, IL-4, IL-6, and IL-13, in basophils stimulated with anti-IgE, N-formyl-methionyl-leucyl-phenylalanine, or phorbol 12-myristate 13-acetate.

Conclusion

Our findings highlight a novel functional activity of ?-MSH, which acts as a natural antiallergic basophil-response modifier. These findings might point to novel therapeutic strategies in treating allergic diseases.

Full text not available from this repository.

More information

e-pub ahead of print date: December 2011
Published date: April 2012
Keywords: basophils, melanocyte-stimulating hormone, melanocortin receptors, neuropeptides
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 338739
URI: https://eprints.soton.ac.uk/id/eprint/338739
ISSN: 0091-6749
PURE UUID: 825b6524-4393-4db9-88c5-5182d17731f9

Catalogue record

Date deposited: 17 May 2012 08:41
Last modified: 16 Jul 2019 22:04

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Contributors

Author: Markus Böhm
Author: Mara Apel
Author: Koji Sugawara
Author: Randolf Brehler
Author: Kerstin Jurk
Author: Thomas A. Luger
Author: Helmut Haas
Author: Ralf Paus
Author: Britta Eiz-Vesper
Author: Andrew F. Walls
Author: Evgeni Ponimaskin
Author: Manuela Gehring
Author: Alexander Kapp
Author: Ulrike Raap

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