Kinhult J, Uddman R, Laan M, Lindén A, Cardell L O
Allergy laboratory, Department of Otorhinolaryngology, Malmö University Hospital, Malmö, Sweden.
Peptides. 2001 Dec;22(12):2151-4. doi: 10.1016/s0196-9781(01)00568-x.
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.
垂体腺苷酸环化酶激活肽38（PACAP 38）是一种神经肽，在哮喘和慢性阻塞性肺疾病等气道疾病中具有多种令人感兴趣的生物学效应。这些效应包括抑制气道和血管平滑肌张力以及调节炎症细胞活性。然而，关于PACAP对粒细胞的影响知之甚少。本研究旨在调查PACAP和密切相关的肽血管活性肠肽（VIP）是否会影响中性粒细胞迁移。使用标准的48孔趋化室来评估PACAP对N-甲酰-L-蛋氨酰-L-亮氨酰-L-苯丙氨酸（fMLP）诱导的中性粒细胞趋化和自发随机迁移的影响。PACAP 38和VIP抑制fMLP诱导的人类中性粒细胞趋化。此外，这两种肽在抑制中性粒细胞自发、未受刺激的迁移方面也呈现出剂量相关趋势。由于据报道细胞室系统中增强的细胞迁移与体内侵袭特性增加相关，PACAP 38对中性粒细胞趋化的抑制作用支持了PACAP具有抗炎作用的观点。这与已充分证明的PACAP的支气管舒张能力一起，可能表明PACAP激动剂在未来哮喘和其他炎症性气道疾病治疗中的作用。
