Annexin 1-derived peptide Ac2-26 inhibits eosinophil recruitment in vivo via decreasing prostaglandin D₂.
BACKGROUND
Asthma is a chronic inflammatory disease of the mucosa and is associated with excess TH₂ cytokines, eotaxin, prostaglandin D₂ (PGD₂) and eosinophilia in the lungs. Previous studies have emphasized that the N-terminal peptide of annexin 1 (peptide Ac2-26) can inhibit mast cell degranulation, antigen-induced eotaxin release as well as the accumulation of both neutrophils and eosinophils in a model of rat pleurisy. The purpose of this study was to demonstrate anti-asthmatic effects of Ac2-26 in an asthma model and to explore possible mechanisms involved.


METHODS
The effect of Ac2-26 on TH₂ cytokine release, eotaxin production, PGD₂ levels and the development of pulmonary eosinophilic inflammation was compared with glucocorticoids in an asthmatic rat model. The study was conducted on rats sensitized and challenged with ovalbumin and plethysmography measured airway responsiveness. Bronchoalveolar lavage (BAL) histopathology and the levels of cytokines, chemokines as well as PGD₂ were examined.


RESULTS
Our results showed that Ac2-26 suppressed the accumulation of eosinophils in airways, reduced IL-4, IL-5, IL-13, PGD₂ and eotaxin levels in the BAL fluid, and lowered the expression of CRTH2. Exogenous PGD₂ significantly attenuated the biological effects of Ac2-26.


CONCLUSIONS
These results indicated that Ac2-26 exerted broad inhibitory effects on airway inflammation and hyperresponsiveness in a rat model of asthma. Exogenous PGD₂ reversed the inhibitory effects of AC2-26 on eosinophil recruitment. Ac2-26 exhibited anti-asthmatic, immunomodulatory activity that was substantially mediated by decreasing PGD₂ production and its CRTH2 receptor expression in vivo.
Wang
Lian-ming
LM
Department of Laboratory Diagnostics, Fourth Affiliated Hospital, Harbin Medical University, Nangang District, Harbin, China.
Li
Wen-hui
WH
Xu
Yong-chen
YC
Wei
Qiang
Q
Zhao
Hong
H
Jiang
Xiao-feng
XF
D000818:Animals; D017305:Annexin A1 / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002452:Cell Count; D016207:Cytokines / Q000032:analysis; D015232:Dinoprostone / Q000037:antagonists & inhibitors* / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology*; D005260:Female; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007150:Immunohistochemistry; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D010991:Plethysmography; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms; D018709:Statistics, Nonparametric
D017305:Annexin A1; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D010455:Peptides; C096153:annexin A1 peptide (2-26); D016210:Methacholine Chloride; D007073:Immunoglobulin E; D015232:Dinoprostone