Modulation of basophil activity

A novel function of the neuropeptide α-melanocyte-stimulating hormone

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

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 α-melanocyte-stimulating hormone (α-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 Ca 2+ 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 α-MSH increased intracellular Ca 2+ but not cyclic AMP levels. α-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 α-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 α-MSH. Moreover, α-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 α-MSH, which acts as a natural antiallergic basophil-response modifier. These findings might point to novel therapeutic strategies in treating allergic diseases.

Original languageEnglish (US)
Pages (from-to)1085-1093
Number of pages9
JournalJournal of Allergy and Clinical Immunology
Volume129
Issue number4
DOIs
StatePublished - Apr 1 2012
Externally publishedYes

Fingerprint

Melanocyte-Stimulating Hormones
Basophils
Neuropeptides
Pro-Opiomelanocortin
N-Formylmethionine Leucyl-Phenylalanine
Cyclic AMP
Agouti Signaling Protein
Acetates
Melanocortin Receptors
Cytokines
Anti-Allergic Agents
Interleukin-13
Pollen
Poaceae
Nose
Interleukin-4
Adrenocorticotropic Hormone
Allergens
Fluorescent Antibody Technique
Interleukin-6

Keywords

  • Basophils
  • melanocortin receptors
  • melanocyte-stimulating hormone
  • neuropeptides

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Modulation of basophil activity : A novel function of the neuropeptide α-melanocyte-stimulating hormone. / 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; Raap, Ulrike.

In: Journal of Allergy and Clinical Immunology, Vol. 129, No. 4, 01.04.2012, p. 1085-1093.

Research output: Contribution to journalArticle

Böhm, M, Apel, M, Sugawara, K, Brehler, R, Jurk, K, Luger, TA, Haas, H, Paus, R, Eiz-Vesper, B, Walls, AF, Ponimaskin, E, Gehring, M, Kapp, A & Raap, U 2012, 'Modulation of basophil activity: A novel function of the neuropeptide α-melanocyte-stimulating hormone', Journal of Allergy and Clinical Immunology, vol. 129, no. 4, pp. 1085-1093. https://doi.org/10.1016/j.jaci.2011.11.012
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 ; Raap, Ulrike. / Modulation of basophil activity : A novel function of the neuropeptide α-melanocyte-stimulating hormone. In: Journal of Allergy and Clinical Immunology. 2012 ; Vol. 129, No. 4. pp. 1085-1093.
@article{fcd5d10af7124338877f95113178c727,
title = "Modulation of basophil activity: A novel function of the neuropeptide α-melanocyte-stimulating hormone",
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 α-melanocyte-stimulating hormone (α-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 Ca 2+ 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 α-MSH increased intracellular Ca 2+ but not cyclic AMP levels. α-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 α-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 α-MSH. Moreover, α-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 α-MSH, which acts as a natural antiallergic basophil-response modifier. These findings might point to novel therapeutic strategies in treating allergic diseases.",
keywords = "Basophils, melanocortin receptors, melanocyte-stimulating hormone, neuropeptides",
author = "Markus B{\"o}hm and Mara Apel and Koji Sugawara and Randolf Brehler and Kerstin Jurk and Luger, {Thomas A.} and Helmut Haas and Ralf Paus and Britta Eiz-Vesper and Walls, {Andrew F.} and Evgeni Ponimaskin and Manuela Gehring and Alexander Kapp and Ulrike Raap",
year = "2012",
month = "4",
day = "1",
doi = "10.1016/j.jaci.2011.11.012",
language = "English (US)",
volume = "129",
pages = "1085--1093",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "4",

}

TY - JOUR

T1 - Modulation of basophil activity

T2 - A novel function of the neuropeptide α-melanocyte-stimulating hormone

AU - Böhm, Markus

AU - Apel, Mara

AU - Sugawara, Koji

AU - Brehler, Randolf

AU - Jurk, Kerstin

AU - Luger, Thomas A.

AU - Haas, Helmut

AU - Paus, Ralf

AU - Eiz-Vesper, Britta

AU - Walls, Andrew F.

AU - Ponimaskin, Evgeni

AU - Gehring, Manuela

AU - Kapp, Alexander

AU - Raap, Ulrike

PY - 2012/4/1

Y1 - 2012/4/1

N2 - 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 α-melanocyte-stimulating hormone (α-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 Ca 2+ 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 α-MSH increased intracellular Ca 2+ but not cyclic AMP levels. α-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 α-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 α-MSH. Moreover, α-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 α-MSH, which acts as a natural antiallergic basophil-response modifier. These findings might point to novel therapeutic strategies in treating allergic diseases.

AB - 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 α-melanocyte-stimulating hormone (α-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 Ca 2+ 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 α-MSH increased intracellular Ca 2+ but not cyclic AMP levels. α-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 α-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 α-MSH. Moreover, α-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 α-MSH, which acts as a natural antiallergic basophil-response modifier. These findings might point to novel therapeutic strategies in treating allergic diseases.

KW - Basophils

KW - melanocortin receptors

KW - melanocyte-stimulating hormone

KW - neuropeptides

UR - http://www.scopus.com/inward/record.url?scp=84859163265&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859163265&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2011.11.012

DO - 10.1016/j.jaci.2011.11.012

M3 - Article

VL - 129

SP - 1085

EP - 1093

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 4

ER -