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Alveolar epithelial type II cells activate alveolar macrophages and mitigate P. Aeruginosa infection.

Kannan S, Huang H, Seeger D, Audet A, Chen Y, Huang C, Gao H, Li S, Wu M - PLoS ONE (2009)

Bottom Line: The ability of phagocytosis and superoxide release by AM was reduced by MCP-1 neutralizing antibodies.Mechanistically, we found that Lyn mediated NFkappaB activation led to increased gene expression and secretion of MCP-1.Collectively, our data indicate that AECII may serve as an immune booster for fighting bacterial infections, particularly in severe immunocompromised conditions.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, University of North Dakota, Grand Forks, North Dakota, USA.

ABSTRACT
Although alveolar epithelial type II cells (AECII) perform substantial roles in the maintenance of alveolar integrity, the extent of their contributions to immune defense is poorly understood. Here, we demonstrate that AECII activates alveolar macrophages (AM) functions, such as phagocytosis using a conditioned medium from AECII infected by P. aeruginosa. AECII-derived chemokine MCP-1, a monocyte chemoattractant protein, was identified as a main factor in enhancing AM function. We proposed that the enhanced immune potency of AECII may play a critical role in alleviation of bacterial propagation and pneumonia. The ability of phagocytosis and superoxide release by AM was reduced by MCP-1 neutralizing antibodies. Furthermore, MCP-1(-/-) mice showed an increased bacterial burden under PAO1 and PAK infection vs. wt littermates. AM from MCP-1(-/-) mice also demonstrated less superoxide and impaired phagocytosis over the controls. In addition, AECII conditioned medium increased the host defense of airway in MCP-1(-/-) mice through the activation of AM function. Mechanistically, we found that Lyn mediated NFkappaB activation led to increased gene expression and secretion of MCP-1. Consequently Lyn(-/-) mice had reduced MCP-1 secretion and resulted in a decrease in superoxide and phagocytosis by AM. Collectively, our data indicate that AECII may serve as an immune booster for fighting bacterial infections, particularly in severe immunocompromised conditions.

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Related in: MedlinePlus

Diagram delineates a pathway involved in the AECII immune role against P. aeruginosa infection.AECII cells initiate an immunity to boost AM anti-infection function. The chemokine MCP-1 seems a crucial factor in this cell-cell cross-talk, which may be initiated by lipid rafts and regulated by Lyn. While boosting MCP-1 production through NFκB pathway, Lyn may contain excessive production of MIP-2α as another mechanism to keep the inflammation response in control.
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pone-0004891-g007: Diagram delineates a pathway involved in the AECII immune role against P. aeruginosa infection.AECII cells initiate an immunity to boost AM anti-infection function. The chemokine MCP-1 seems a crucial factor in this cell-cell cross-talk, which may be initiated by lipid rafts and regulated by Lyn. While boosting MCP-1 production through NFκB pathway, Lyn may contain excessive production of MIP-2α as another mechanism to keep the inflammation response in control.

Mentions: The AECII – AM cross-talk is presented in a simplified model (Figure 7). Bacterial infection activates AECII cells that secrete chemokines (MCP-1). MCP-1 transmits signals to activate AM, which migrate towards infection sites and eliminate the pathogen. Lyn and lipid rafts may regulate MCP-1 and AM activation. In addition, the host defense may be balanced through the fine regulation by both Lyn and MCP-1.


Alveolar epithelial type II cells activate alveolar macrophages and mitigate P. Aeruginosa infection.

Kannan S, Huang H, Seeger D, Audet A, Chen Y, Huang C, Gao H, Li S, Wu M - PLoS ONE (2009)

Diagram delineates a pathway involved in the AECII immune role against P. aeruginosa infection.AECII cells initiate an immunity to boost AM anti-infection function. The chemokine MCP-1 seems a crucial factor in this cell-cell cross-talk, which may be initiated by lipid rafts and regulated by Lyn. While boosting MCP-1 production through NFκB pathway, Lyn may contain excessive production of MIP-2α as another mechanism to keep the inflammation response in control.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2654511&req=5

pone-0004891-g007: Diagram delineates a pathway involved in the AECII immune role against P. aeruginosa infection.AECII cells initiate an immunity to boost AM anti-infection function. The chemokine MCP-1 seems a crucial factor in this cell-cell cross-talk, which may be initiated by lipid rafts and regulated by Lyn. While boosting MCP-1 production through NFκB pathway, Lyn may contain excessive production of MIP-2α as another mechanism to keep the inflammation response in control.
Mentions: The AECII – AM cross-talk is presented in a simplified model (Figure 7). Bacterial infection activates AECII cells that secrete chemokines (MCP-1). MCP-1 transmits signals to activate AM, which migrate towards infection sites and eliminate the pathogen. Lyn and lipid rafts may regulate MCP-1 and AM activation. In addition, the host defense may be balanced through the fine regulation by both Lyn and MCP-1.

Bottom Line: The ability of phagocytosis and superoxide release by AM was reduced by MCP-1 neutralizing antibodies.Mechanistically, we found that Lyn mediated NFkappaB activation led to increased gene expression and secretion of MCP-1.Collectively, our data indicate that AECII may serve as an immune booster for fighting bacterial infections, particularly in severe immunocompromised conditions.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, University of North Dakota, Grand Forks, North Dakota, USA.

ABSTRACT
Although alveolar epithelial type II cells (AECII) perform substantial roles in the maintenance of alveolar integrity, the extent of their contributions to immune defense is poorly understood. Here, we demonstrate that AECII activates alveolar macrophages (AM) functions, such as phagocytosis using a conditioned medium from AECII infected by P. aeruginosa. AECII-derived chemokine MCP-1, a monocyte chemoattractant protein, was identified as a main factor in enhancing AM function. We proposed that the enhanced immune potency of AECII may play a critical role in alleviation of bacterial propagation and pneumonia. The ability of phagocytosis and superoxide release by AM was reduced by MCP-1 neutralizing antibodies. Furthermore, MCP-1(-/-) mice showed an increased bacterial burden under PAO1 and PAK infection vs. wt littermates. AM from MCP-1(-/-) mice also demonstrated less superoxide and impaired phagocytosis over the controls. In addition, AECII conditioned medium increased the host defense of airway in MCP-1(-/-) mice through the activation of AM function. Mechanistically, we found that Lyn mediated NFkappaB activation led to increased gene expression and secretion of MCP-1. Consequently Lyn(-/-) mice had reduced MCP-1 secretion and resulted in a decrease in superoxide and phagocytosis by AM. Collectively, our data indicate that AECII may serve as an immune booster for fighting bacterial infections, particularly in severe immunocompromised conditions.

Show MeSH
Related in: MedlinePlus