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Ac2-26 Mimetic Peptide of Annexin A1 Inhibits Local and Systemic Inflammatory Processes Induced by Bothrops moojeni Venom and the Lys-49 Phospholipase A2 in a Rat Model.

Stuqui B, de Paula-Silva M, Carlos CP, Ullah A, Arni RK, Gil CD, Oliani SM - PLoS ONE (2015)

Bottom Line: In the kidneys, CV and MjTX-II administrations were associated with an increased number of macrophages and morphological alterations in the juxtamedullary nephrons in proximal and distal tubules.Ac2-26 promoted significant recovery of the juxtamedullary structures, decreased the number of macrophages and diminished the AnxA1 in epithelial cells from distal tubules and renal capsules.Our results show that Ac2-26 treatment significantly attenuates local and systemic inflammatory processes and indicate this peptide as a potential target for the development of new therapeutic strategies for the snakebite envenomation treatment.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunomorphology, Department of Biology, São Paulo State University (UNESP), São José do Rio Preto, São Paulo, Brazil.

ABSTRACT
Annexin A1 (AnxA1) is an endogenous glucocorticoid regulated protein that modulates anti-inflammatory process and its therapeutic potential has recently been recognized in a range of systemic inflammatory disorders. The effect of the N-terminal peptide Ac2-26 of AnxA1 on the toxic activities of Bothrops moojeni crude venom (CV) and its myotoxin II (MjTX-II) were evaluated using a peritonitis rat model. Peritonitis was induced by the intraperitoneal injection of either CV or MjTX-II, a Lys-49 phospholipase A2. Fifteen minutes after the injection, the rats were treated with either Ac2-26 or PBS. Four hours later, the CV and MjTX-II-induced peritonitis were characterized by neutrophilia (in the peritoneal exudate, blood and mesentery) and increased number of mesenteric degranulated mast cells and macrophages. At 24 hours post-injection, the local inflammatory response was attenuated in the CV-induced peritonitis while the MjTX-II group exhibited neutrophilia (peritoneal exudates and blood). Ac2-26 treatment prevented the influx of neutrophils in MjTX-II-induced peritonitis and diminished the proportion of mesenteric degranulated mast cells and macrophages in CV-induced peritonitis. Additionally, CV and MjTX-II promoted increased levels of IL-1β and IL-6 in the peritoneal exudates which were significantly reduced after Ac2-26 treatment. At 4 and 24 hours, the endogenous expression of AnxA1 was upregulated in the mesenteric neutrophils (CV and MjTX-II groups) and mast cells (CV group). In the kidneys, CV and MjTX-II administrations were associated with an increased number of macrophages and morphological alterations in the juxtamedullary nephrons in proximal and distal tubules. Ac2-26 promoted significant recovery of the juxtamedullary structures, decreased the number of macrophages and diminished the AnxA1 in epithelial cells from distal tubules and renal capsules. Our results show that Ac2-26 treatment significantly attenuates local and systemic inflammatory processes and indicate this peptide as a potential target for the development of new therapeutic strategies for the snakebite envenomation treatment.

No MeSH data available.


Related in: MedlinePlus

Analysis of AnxA1 expression in the juxtamedullary renal structures.AnxA1 immunostaining was detected in the epithelial cells under all of the experimental conditions (A, C, E, G, I), concentrated in the glomerular capsule (arrows) and distal convuluted tubules (asterisks). Ac2-26 post-treatment decreased the immunostaining for endogenous AnxA1 in the distal tubules and glomerular capsule (D, F, H, J) 4 and 24 h after CV- and MjTX-II-induced peritonitis. Negative control of the reaction (B). Counterstain: hematoxylin. Scale bars: 20 μm. Densitometric analysis of the epithelial cells from distal convuluted tubules (K-L) and glomerular capsule (M-N) immunostained for AnxA1. Values (arbitrary units) are expressed as the mean ± SEM of sections analyzed from 5 rats /group. **P < 0.01 and ***P < 0.001 vs control; ###P < 0.001 vs CV groups; §§P < 0.01 and §§§P < 0.001 vs MjTX-II groups at the corresponding experimental time.
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pone.0130803.g007: Analysis of AnxA1 expression in the juxtamedullary renal structures.AnxA1 immunostaining was detected in the epithelial cells under all of the experimental conditions (A, C, E, G, I), concentrated in the glomerular capsule (arrows) and distal convuluted tubules (asterisks). Ac2-26 post-treatment decreased the immunostaining for endogenous AnxA1 in the distal tubules and glomerular capsule (D, F, H, J) 4 and 24 h after CV- and MjTX-II-induced peritonitis. Negative control of the reaction (B). Counterstain: hematoxylin. Scale bars: 20 μm. Densitometric analysis of the epithelial cells from distal convuluted tubules (K-L) and glomerular capsule (M-N) immunostained for AnxA1. Values (arbitrary units) are expressed as the mean ± SEM of sections analyzed from 5 rats /group. **P < 0.01 and ***P < 0.001 vs control; ###P < 0.001 vs CV groups; §§P < 0.01 and §§§P < 0.001 vs MjTX-II groups at the corresponding experimental time.

Mentions: Endogenous AnxA1 immunostaining was analyzed in the juxtamedullary nephrons in all experimental groups and its expression was detected in epithelial cells, especially from the glomerular capsule and distal convoluted tubules (Fig 7).


Ac2-26 Mimetic Peptide of Annexin A1 Inhibits Local and Systemic Inflammatory Processes Induced by Bothrops moojeni Venom and the Lys-49 Phospholipase A2 in a Rat Model.

Stuqui B, de Paula-Silva M, Carlos CP, Ullah A, Arni RK, Gil CD, Oliani SM - PLoS ONE (2015)

Analysis of AnxA1 expression in the juxtamedullary renal structures.AnxA1 immunostaining was detected in the epithelial cells under all of the experimental conditions (A, C, E, G, I), concentrated in the glomerular capsule (arrows) and distal convuluted tubules (asterisks). Ac2-26 post-treatment decreased the immunostaining for endogenous AnxA1 in the distal tubules and glomerular capsule (D, F, H, J) 4 and 24 h after CV- and MjTX-II-induced peritonitis. Negative control of the reaction (B). Counterstain: hematoxylin. Scale bars: 20 μm. Densitometric analysis of the epithelial cells from distal convuluted tubules (K-L) and glomerular capsule (M-N) immunostained for AnxA1. Values (arbitrary units) are expressed as the mean ± SEM of sections analyzed from 5 rats /group. **P < 0.01 and ***P < 0.001 vs control; ###P < 0.001 vs CV groups; §§P < 0.01 and §§§P < 0.001 vs MjTX-II groups at the corresponding experimental time.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492549&req=5

pone.0130803.g007: Analysis of AnxA1 expression in the juxtamedullary renal structures.AnxA1 immunostaining was detected in the epithelial cells under all of the experimental conditions (A, C, E, G, I), concentrated in the glomerular capsule (arrows) and distal convuluted tubules (asterisks). Ac2-26 post-treatment decreased the immunostaining for endogenous AnxA1 in the distal tubules and glomerular capsule (D, F, H, J) 4 and 24 h after CV- and MjTX-II-induced peritonitis. Negative control of the reaction (B). Counterstain: hematoxylin. Scale bars: 20 μm. Densitometric analysis of the epithelial cells from distal convuluted tubules (K-L) and glomerular capsule (M-N) immunostained for AnxA1. Values (arbitrary units) are expressed as the mean ± SEM of sections analyzed from 5 rats /group. **P < 0.01 and ***P < 0.001 vs control; ###P < 0.001 vs CV groups; §§P < 0.01 and §§§P < 0.001 vs MjTX-II groups at the corresponding experimental time.
Mentions: Endogenous AnxA1 immunostaining was analyzed in the juxtamedullary nephrons in all experimental groups and its expression was detected in epithelial cells, especially from the glomerular capsule and distal convoluted tubules (Fig 7).

Bottom Line: In the kidneys, CV and MjTX-II administrations were associated with an increased number of macrophages and morphological alterations in the juxtamedullary nephrons in proximal and distal tubules.Ac2-26 promoted significant recovery of the juxtamedullary structures, decreased the number of macrophages and diminished the AnxA1 in epithelial cells from distal tubules and renal capsules.Our results show that Ac2-26 treatment significantly attenuates local and systemic inflammatory processes and indicate this peptide as a potential target for the development of new therapeutic strategies for the snakebite envenomation treatment.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunomorphology, Department of Biology, São Paulo State University (UNESP), São José do Rio Preto, São Paulo, Brazil.

ABSTRACT
Annexin A1 (AnxA1) is an endogenous glucocorticoid regulated protein that modulates anti-inflammatory process and its therapeutic potential has recently been recognized in a range of systemic inflammatory disorders. The effect of the N-terminal peptide Ac2-26 of AnxA1 on the toxic activities of Bothrops moojeni crude venom (CV) and its myotoxin II (MjTX-II) were evaluated using a peritonitis rat model. Peritonitis was induced by the intraperitoneal injection of either CV or MjTX-II, a Lys-49 phospholipase A2. Fifteen minutes after the injection, the rats were treated with either Ac2-26 or PBS. Four hours later, the CV and MjTX-II-induced peritonitis were characterized by neutrophilia (in the peritoneal exudate, blood and mesentery) and increased number of mesenteric degranulated mast cells and macrophages. At 24 hours post-injection, the local inflammatory response was attenuated in the CV-induced peritonitis while the MjTX-II group exhibited neutrophilia (peritoneal exudates and blood). Ac2-26 treatment prevented the influx of neutrophils in MjTX-II-induced peritonitis and diminished the proportion of mesenteric degranulated mast cells and macrophages in CV-induced peritonitis. Additionally, CV and MjTX-II promoted increased levels of IL-1β and IL-6 in the peritoneal exudates which were significantly reduced after Ac2-26 treatment. At 4 and 24 hours, the endogenous expression of AnxA1 was upregulated in the mesenteric neutrophils (CV and MjTX-II groups) and mast cells (CV group). In the kidneys, CV and MjTX-II administrations were associated with an increased number of macrophages and morphological alterations in the juxtamedullary nephrons in proximal and distal tubules. Ac2-26 promoted significant recovery of the juxtamedullary structures, decreased the number of macrophages and diminished the AnxA1 in epithelial cells from distal tubules and renal capsules. Our results show that Ac2-26 treatment significantly attenuates local and systemic inflammatory processes and indicate this peptide as a potential target for the development of new therapeutic strategies for the snakebite envenomation treatment.

No MeSH data available.


Related in: MedlinePlus