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EphA2 Receptor Signaling Mediates Inflammatory Responses in Lipopolysaccharide-Induced Lung Injury.

Hong JY, Shin MH, Chung KS, Kim EY, Jung JY, Kang YA, Kim YS, Kim SK, Chang J, Park MS - Tuberc Respir Dis (Seoul) (2015)

Bottom Line: IgG+LPS: 1.38±1.08 mg/mL; p=0.192) were decreased in EphA2 mAb+LPS group, as compared to the IgG+LPS group.In addition, EphA2 antagonism reduced the expression of phospho-p85, phosphoinositide 3-kinase 110γ, phospho-Akt, nuclear factor κB, and proinflammatory cytokines.Furthermore, EphA2 antagonism inhibits the phosphoinositide 3-kinase-Akt pathway and attenuates inflammation.

View Article: PubMed Central - PubMed

Affiliation: Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

ABSTRACT

Background: Eph receptors and ephrin ligands have several functions including angiogenesis, cell migration, axon guidance, fluid homeostasis, oncogenesis, inflammation and injury repair. The EphA2 receptor potentially mediates the regulation of vascular permeability and inflammation in response to lung injury.

Methods: Mice were divided into 3 experimental groups to study the role of EphA2 signaling in the lipopolysaccharide (LPS)-induced lung injury model i.e., IgG+phosphate-buffered saline (PBS) group (IgG instillation before PBS exposure), IgG+LPS group (IgG instillation before LPS exposure) and EphA2 monoclonal antibody (mAb)+LPS group (EphA2 mAb pretreatment before LPS exposure).

Results: EphA2 and ephrinA1 were upregulated in LPS-induced lung injury. The lung injury score of the EphA2 mAb+LPS group was lower than that of the IgG+LPS group (4.30±2.93 vs. 11.45±1.20, respectively; p=0.004). Cell counts (EphA2 mAb+LPS: 11.33×10(4)±8.84×10(4) vs. IgG+LPS: 208.0×10(4)±122.6×10(4); p=0.018) and total protein concentrations (EphA2 mAb+LPS: 0.52±0.41 mg/mL vs. IgG+LPS: 1.38±1.08 mg/mL; p=0.192) were decreased in EphA2 mAb+LPS group, as compared to the IgG+LPS group. In addition, EphA2 antagonism reduced the expression of phospho-p85, phosphoinositide 3-kinase 110γ, phospho-Akt, nuclear factor κB, and proinflammatory cytokines.

Conclusion: This results of the study indicated a role for EphA2-ephrinA1 signaling in the pathogenesis of LPS-induced lung injury. Furthermore, EphA2 antagonism inhibits the phosphoinositide 3-kinase-Akt pathway and attenuates inflammation.

No MeSH data available.


Related in: MedlinePlus

The effect of EphA2 monoclonal antibody pretreatment in lipopolysaccharide (LPS)-induced lung injury. Mice were intranasally treated with IgG or EphA2 antibody. One hour later, they were intranasally treated with phosphate buffered saline (PBS) or 40 µg LPS in PBS. The lungs were removed after 24 hr and stained with hematoxylin and eosin (H&E). (A) IgG+PBS group, (B) IgG+LPS group, (C) EphA2 Ab 2 µg+LPS group, and (D) EphA2 Ab 4 µg+LPS group, n=4 per group. The IgG+LPS group (B) showed obvious neutrophil infiltration and alveolar septal infiltration; however, the EphA2 Ab+LPS groups (C, D) showed attenuated lung injury (H&E stain, ×400).
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Figure 2: The effect of EphA2 monoclonal antibody pretreatment in lipopolysaccharide (LPS)-induced lung injury. Mice were intranasally treated with IgG or EphA2 antibody. One hour later, they were intranasally treated with phosphate buffered saline (PBS) or 40 µg LPS in PBS. The lungs were removed after 24 hr and stained with hematoxylin and eosin (H&E). (A) IgG+PBS group, (B) IgG+LPS group, (C) EphA2 Ab 2 µg+LPS group, and (D) EphA2 Ab 4 µg+LPS group, n=4 per group. The IgG+LPS group (B) showed obvious neutrophil infiltration and alveolar septal infiltration; however, the EphA2 Ab+LPS groups (C, D) showed attenuated lung injury (H&E stain, ×400).

Mentions: In the IgG+PBS group, neutrophil recruitment, alveolar wall thickening and hemorrhage were not observed, contrary to the results of the IgG+LPS group (Figure 2A), where hyaline membrane formation, neutrophils in the alveolar and interstitium space and thickening of alveolar septa were remarkably increased (Figure 2B). The EphA2 mAb+LPS groups demonstrated reduced neutrophil infiltration and alveolar thickening compared with the IgG+LPS group (Figure 2C, D).


EphA2 Receptor Signaling Mediates Inflammatory Responses in Lipopolysaccharide-Induced Lung Injury.

Hong JY, Shin MH, Chung KS, Kim EY, Jung JY, Kang YA, Kim YS, Kim SK, Chang J, Park MS - Tuberc Respir Dis (Seoul) (2015)

The effect of EphA2 monoclonal antibody pretreatment in lipopolysaccharide (LPS)-induced lung injury. Mice were intranasally treated with IgG or EphA2 antibody. One hour later, they were intranasally treated with phosphate buffered saline (PBS) or 40 µg LPS in PBS. The lungs were removed after 24 hr and stained with hematoxylin and eosin (H&E). (A) IgG+PBS group, (B) IgG+LPS group, (C) EphA2 Ab 2 µg+LPS group, and (D) EphA2 Ab 4 µg+LPS group, n=4 per group. The IgG+LPS group (B) showed obvious neutrophil infiltration and alveolar septal infiltration; however, the EphA2 Ab+LPS groups (C, D) showed attenuated lung injury (H&E stain, ×400).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4499589&req=5

Figure 2: The effect of EphA2 monoclonal antibody pretreatment in lipopolysaccharide (LPS)-induced lung injury. Mice were intranasally treated with IgG or EphA2 antibody. One hour later, they were intranasally treated with phosphate buffered saline (PBS) or 40 µg LPS in PBS. The lungs were removed after 24 hr and stained with hematoxylin and eosin (H&E). (A) IgG+PBS group, (B) IgG+LPS group, (C) EphA2 Ab 2 µg+LPS group, and (D) EphA2 Ab 4 µg+LPS group, n=4 per group. The IgG+LPS group (B) showed obvious neutrophil infiltration and alveolar septal infiltration; however, the EphA2 Ab+LPS groups (C, D) showed attenuated lung injury (H&E stain, ×400).
Mentions: In the IgG+PBS group, neutrophil recruitment, alveolar wall thickening and hemorrhage were not observed, contrary to the results of the IgG+LPS group (Figure 2A), where hyaline membrane formation, neutrophils in the alveolar and interstitium space and thickening of alveolar septa were remarkably increased (Figure 2B). The EphA2 mAb+LPS groups demonstrated reduced neutrophil infiltration and alveolar thickening compared with the IgG+LPS group (Figure 2C, D).

Bottom Line: IgG+LPS: 1.38±1.08 mg/mL; p=0.192) were decreased in EphA2 mAb+LPS group, as compared to the IgG+LPS group.In addition, EphA2 antagonism reduced the expression of phospho-p85, phosphoinositide 3-kinase 110γ, phospho-Akt, nuclear factor κB, and proinflammatory cytokines.Furthermore, EphA2 antagonism inhibits the phosphoinositide 3-kinase-Akt pathway and attenuates inflammation.

View Article: PubMed Central - PubMed

Affiliation: Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

ABSTRACT

Background: Eph receptors and ephrin ligands have several functions including angiogenesis, cell migration, axon guidance, fluid homeostasis, oncogenesis, inflammation and injury repair. The EphA2 receptor potentially mediates the regulation of vascular permeability and inflammation in response to lung injury.

Methods: Mice were divided into 3 experimental groups to study the role of EphA2 signaling in the lipopolysaccharide (LPS)-induced lung injury model i.e., IgG+phosphate-buffered saline (PBS) group (IgG instillation before PBS exposure), IgG+LPS group (IgG instillation before LPS exposure) and EphA2 monoclonal antibody (mAb)+LPS group (EphA2 mAb pretreatment before LPS exposure).

Results: EphA2 and ephrinA1 were upregulated in LPS-induced lung injury. The lung injury score of the EphA2 mAb+LPS group was lower than that of the IgG+LPS group (4.30±2.93 vs. 11.45±1.20, respectively; p=0.004). Cell counts (EphA2 mAb+LPS: 11.33×10(4)±8.84×10(4) vs. IgG+LPS: 208.0×10(4)±122.6×10(4); p=0.018) and total protein concentrations (EphA2 mAb+LPS: 0.52±0.41 mg/mL vs. IgG+LPS: 1.38±1.08 mg/mL; p=0.192) were decreased in EphA2 mAb+LPS group, as compared to the IgG+LPS group. In addition, EphA2 antagonism reduced the expression of phospho-p85, phosphoinositide 3-kinase 110γ, phospho-Akt, nuclear factor κB, and proinflammatory cytokines.

Conclusion: This results of the study indicated a role for EphA2-ephrinA1 signaling in the pathogenesis of LPS-induced lung injury. Furthermore, EphA2 antagonism inhibits the phosphoinositide 3-kinase-Akt pathway and attenuates inflammation.

No MeSH data available.


Related in: MedlinePlus