Limits...
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

Presence of renal macrophages after MjTX-II-induced peritonitis.An increased number of cells was observed in the glomeruli (arrows) and interstice (arrowheads) of the juxtamedullary region 24 h after peritonitis induced by MjTX-II (B), compared to the control group (A). Ac2-26 peptide post-treatment prevented the macrophages influx in renal tissue (C). Scale bars: 20 μm. Counterstain: Hematoxylin. The data represent the mean ± SEM of the number of interstitial (D) and glomerular (E) macrophages per 20 fields in the renal tissue (n = 5 animals/group). **P < 0.01 and ***P < 0.001 vs control; §P < 0.05 and §§P < 0.01 vs MjTX-II 24 h.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4492549&req=5

pone.0130803.g006: Presence of renal macrophages after MjTX-II-induced peritonitis.An increased number of cells was observed in the glomeruli (arrows) and interstice (arrowheads) of the juxtamedullary region 24 h after peritonitis induced by MjTX-II (B), compared to the control group (A). Ac2-26 peptide post-treatment prevented the macrophages influx in renal tissue (C). Scale bars: 20 μm. Counterstain: Hematoxylin. The data represent the mean ± SEM of the number of interstitial (D) and glomerular (E) macrophages per 20 fields in the renal tissue (n = 5 animals/group). **P < 0.01 and ***P < 0.001 vs control; §P < 0.05 and §§P < 0.01 vs MjTX-II 24 h.

Mentions: In addition to the morphological alterations, we observed that the administration of MjTX-II caused a marked influx of macrophages into the renal glomerulus and interstitium (Fig 6) at 24 hours, as detected by anti-ED-1 antibodies. The treatment with Ac2-26 peptide efficiently decreased the numbers of macrophages in both renal compartments in the MjTX-II group at 24 hours (Fig 6C–6E), but not in the CV group, suggesting an inhibitory regulation of monocyte recruitment into the tissue.


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)

Presence of renal macrophages after MjTX-II-induced peritonitis.An increased number of cells was observed in the glomeruli (arrows) and interstice (arrowheads) of the juxtamedullary region 24 h after peritonitis induced by MjTX-II (B), compared to the control group (A). Ac2-26 peptide post-treatment prevented the macrophages influx in renal tissue (C). Scale bars: 20 μm. Counterstain: Hematoxylin. The data represent the mean ± SEM of the number of interstitial (D) and glomerular (E) macrophages per 20 fields in the renal tissue (n = 5 animals/group). **P < 0.01 and ***P < 0.001 vs control; §P < 0.05 and §§P < 0.01 vs MjTX-II 24 h.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0130803.g006: Presence of renal macrophages after MjTX-II-induced peritonitis.An increased number of cells was observed in the glomeruli (arrows) and interstice (arrowheads) of the juxtamedullary region 24 h after peritonitis induced by MjTX-II (B), compared to the control group (A). Ac2-26 peptide post-treatment prevented the macrophages influx in renal tissue (C). Scale bars: 20 μm. Counterstain: Hematoxylin. The data represent the mean ± SEM of the number of interstitial (D) and glomerular (E) macrophages per 20 fields in the renal tissue (n = 5 animals/group). **P < 0.01 and ***P < 0.001 vs control; §P < 0.05 and §§P < 0.01 vs MjTX-II 24 h.
Mentions: In addition to the morphological alterations, we observed that the administration of MjTX-II caused a marked influx of macrophages into the renal glomerulus and interstitium (Fig 6) at 24 hours, as detected by anti-ED-1 antibodies. The treatment with Ac2-26 peptide efficiently decreased the numbers of macrophages in both renal compartments in the MjTX-II group at 24 hours (Fig 6C–6E), but not in the CV group, suggesting an inhibitory regulation of monocyte recruitment into the tissue.

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