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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Dermatology, University of Münster, Münster, Germany. bohmm@uni-muenster.de
authors.forename: Markus
authors.initials: M
authors.lastname: Böhm
authors.forename: Mara
authors.initials: M
authors.lastname: Apel
authors.forename: Koji
authors.initials: K
authors.lastname: Sugawara
authors.forename: Randolf
authors.initials: R
authors.lastname: Brehler
authors.forename: Kerstin
authors.initials: K
authors.lastname: Jurk
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Luger
authors.forename: Helmut
authors.initials: H
authors.lastname: Haas
authors.forename: Ralf
authors.initials: R
authors.lastname: Paus
authors.forename: Britta
authors.initials: B
authors.lastname: Eiz-Vesper
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Walls
authors.forename: Evgeni
authors.initials: E
authors.lastname: Ponimaskin
authors.forename: Manuela
authors.initials: M
authors.lastname: Gehring
authors.forename: Alexander
authors.initials: A
authors.lastname: Kapp
authors.forename: Ulrike
authors.initials: U
authors.lastname: Raap
mesh_terms: D000485:Allergens / Q000276:immunology; D001491:Basophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D011333:Pro-Opiomelanocortin / Q000235:genetics; D044101:Receptors, Melanocortin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic; D000521:alpha-MSH / Q000494:pharmacology*
chemical_list: D000485:Allergens; D016207:Cytokines; D044101:Receptors, Melanocortin; D000521:alpha-MSH; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011333:Pro-Opiomelanocortin; D000242:Cyclic AMP