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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

Expression of AnxA1 in the mesenteric neutrophils.Strong AnxA1 immunoreactivity in neutrophils (arrows) from CV (B, C) and MjTX-II (E, F) groups, after 4 and 24 h, compared with cells of control group (A). The absence of immunoreactivity in the negative control (D). Scale bars: 5 μm. Counterstain: hematoxylin. Densitometric analysis of mesenteric neutrophils immunostained for AnxA1 in the CV (G) and MjTX-II (H) groups. The values (arbitrary units) are expressed as mean ± SEM of the sections analyzed from 5 rats /group. **P < 0.01 and ***P < 0.001 vs control.
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pone.0130803.g003: Expression of AnxA1 in the mesenteric neutrophils.Strong AnxA1 immunoreactivity in neutrophils (arrows) from CV (B, C) and MjTX-II (E, F) groups, after 4 and 24 h, compared with cells of control group (A). The absence of immunoreactivity in the negative control (D). Scale bars: 5 μm. Counterstain: hematoxylin. Densitometric analysis of mesenteric neutrophils immunostained for AnxA1 in the CV (G) and MjTX-II (H) groups. The values (arbitrary units) are expressed as mean ± SEM of the sections analyzed from 5 rats /group. **P < 0.01 and ***P < 0.001 vs control.

Mentions: After 4 and 24 hours of either CV or MjTX-II administration, we observed extravasated neutrophils and intense AnxA1 immunoreactivity compared to the control group (Fig 3A–3C, 3E and 3F). We did not detected immunostaining in the cells used as a negative control (Fig 3D). These histological observations were confirmed by densitometric analysis of AnxA1 (Fig 3G and 3H).


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)

Expression of AnxA1 in the mesenteric neutrophils.Strong AnxA1 immunoreactivity in neutrophils (arrows) from CV (B, C) and MjTX-II (E, F) groups, after 4 and 24 h, compared with cells of control group (A). The absence of immunoreactivity in the negative control (D). Scale bars: 5 μm. Counterstain: hematoxylin. Densitometric analysis of mesenteric neutrophils immunostained for AnxA1 in the CV (G) and MjTX-II (H) groups. The values (arbitrary units) are expressed as mean ± SEM of the sections analyzed from 5 rats /group. **P < 0.01 and ***P < 0.001 vs control.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0130803.g003: Expression of AnxA1 in the mesenteric neutrophils.Strong AnxA1 immunoreactivity in neutrophils (arrows) from CV (B, C) and MjTX-II (E, F) groups, after 4 and 24 h, compared with cells of control group (A). The absence of immunoreactivity in the negative control (D). Scale bars: 5 μm. Counterstain: hematoxylin. Densitometric analysis of mesenteric neutrophils immunostained for AnxA1 in the CV (G) and MjTX-II (H) groups. The values (arbitrary units) are expressed as mean ± SEM of the sections analyzed from 5 rats /group. **P < 0.01 and ***P < 0.001 vs control.
Mentions: After 4 and 24 hours of either CV or MjTX-II administration, we observed extravasated neutrophils and intense AnxA1 immunoreactivity compared to the control group (Fig 3A–3C, 3E and 3F). We did not detected immunostaining in the cells used as a negative control (Fig 3D). These histological observations were confirmed by densitometric analysis of AnxA1 (Fig 3G and 3H).

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