title: Pituitary adenylate cyclase-activating peptide inhibits neutrophil chemotaxis.
abstract: Pituitary adenylate cyclase-activating peptide 38 (PACAP 38) is a neuropeptide that displays several biological effects of interest in the context of airway diseases such as asthma and chronic obstructive pulmonary disease. These effects include inhibition of airway and vascular smooth muscle tone as well as modulation of inflammatory cell activity. However, little is known about the effect of PACAP on granulocytes. The present study was designed to investigate if PACAP and the closely related peptide vasoactive intestinal peptide (VIP) could affect neutrophil migration. A standard 48 well chemotaxis chamber was used to assess the effects of PACAP on N-Formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP)-induced neutrophil chemotaxis and spontaneous random migration. PACAP 38 and VIP inhibited fMLP-induced human neutrophil chemotaxis. Furthermore, both peptides also exhibited a dose-related trend toward inhibiting the spontaneous, unstimulated migration of neutrophils. Since enhanced cell migration in cell chamber systems is reported to correlate with increased invasive properties in vivo, the presented inhibitory effects of PACAP 38 on neutrophil chemotaxis, supports the idea of an anti-inflammatory role for PACAP. This together with the well documented bronchodilatory capacity of PACAP might indicate a role for PACAP-agonists in future treatment of asthma and other inflammatory airway diseases.
authors.affiliation: Allergy laboratory, Department of Otorhinolaryngology, Malmö University Hospital, Malmö, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Kinhult
authors.forename: R
authors.initials: R
authors.lastname: Uddman
authors.forename: M
authors.initials: M
authors.lastname: Laan
authors.forename: A
authors.initials: A
authors.lastname: Lindén
authors.forename: L O
authors.initials: LO
authors.lastname: Cardell
mesh_terms: D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009479:Neuropeptides / Q000494:pharmacology*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide
chemical_list: C495401:ADCYAP1 protein, human; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D009240:N-Formylmethionine Leucyl-Phenylalanine