A novel effect for annexin 1-derived peptide ac2-26: reduction of allergic inflammation in the rat.
Previous investigations have provided evidence that the N-terminal peptide of annexin 1 (peptide Ac2-26) has the capacity of reproducing the anti-inflammatory actions of the full-length protein in many systems. In the current study, we report the effectiveness of the peptide Ac2-26 as an antiallergic tool in a model of rat pleurisy and provide indication for some of the mechanisms involved. In rats inflamed by injection of ovalbumin into the pleural cavity 14 days postsensitization, peptide Ac2-26 (50-200 microg/cavity) inhibited mast cell degranulation, plasma protein leakage, and the accumulation of both neutrophils and eosinophils. Treatment with either peptide Ac2-26 (200 microg/cavity) or dexamethasone (1 mg/kg i.p.) inhibited ovalbumin-induced eotaxin release in the pleural effluents. In vitro, peptide Ac2-26 inhibited ovalbumin-evoked histamine release from subcutaneous tissue fragments obtained from sensitized rats (33-66 microM) and interleukin-13-evoked eotaxin generation from cultured rat mesothelial cells (16-33 microM) but not eosinophil chemotaxis. This work demonstrates that the annexin 1 mimetic peptide Ac2-26 prevents allergen-evoked eosinophilic inflammatory response in rats. Combined analysis of the in vivo and in vitro experiments presented herein suggests that the blockade of secretion of pivotal mediators for the allergic response, such as histamine and eotaxin, could be responsible for the inhibitory actions displayed by peptide Ac2-26.
Bandeira-Melo
Christianne
C
Department of Physiology and Pharmacodinamics, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Manguinhos, Rio de Janeiro, Brazil.
Bonavita
André Gustavo C
AG
Diaz
Bruno L
BL
E Silva
Patricia M R
PM
Carvalho
Vinícius F
VF
Jose
Peter J
PJ
Flower
Roderick J
RJ
Perretti
Mauro
M
Martins
Marco A
MA
D000818:Animals; D017305:Annexin A1 / Q000494:pharmacology*; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D015550:Cell Degranulation / Q000187:drug effects; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000096:biosynthesis; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D005260:Female; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides; D010998:Pleurisy / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar
D017305:Annexin A1; D018926:Anti-Allergic Agents; C515458:Ccl11 protein, rat; D054413:Chemokine CCL11; D019742:Chemokines, CC; D010446:Peptide Fragments; D010455:Peptides; C096153:annexin A1 peptide (2-26)