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Role of T cells in a gp91phox knockout murine model of acute allergic asthma.

Banerjee ER, Henderson WR - Allergy Asthma Clin Immunol (2013)

Bottom Line: Molecular regulation of inflammation, especially, the role of effector cells in NADPH oxidase-mediated redox reactions for producing O2- (superoxide anion) is a critical step.Materials and Methods and Treatment: To clarify the role of NADPH oxidase in the pathophysiology of T cell-initiatedmacrophage-associated allergic asthma, we induced allergen dependent inflammation in a gp91phox-/- SKO (single knockout) and a gp91phox-/- MMP-12-/- DKO (double knockout) mouse and analysed trafficking and functionality of various cell types, the T cell function and T cell-macrophage interaction being given special emphasis.Composite asthma symptoms expressed in a more aggravated manner in both the KO (SKO and DKO) mice compared to WT indicating that some redundancy may exist in the response pathways of gp91phox and MMP-12.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine, Division of Allergy and Infectious Diseases, Center for Allergy and Inflammation, University of Washington, Room 254, 850 Republican Street, Seattle, WA 98109, USA. enarb1@gmail.com.

ABSTRACT

Objective: Molecular regulation of inflammation, especially, the role of effector cells in NADPH oxidase-mediated redox reactions for producing O2- (superoxide anion) is a critical step. This study explores the roles of macrophages and neutrophils and their cross-talk with extra-cellular matrix components in the light of the role essayed by T cells. Materials and Methods and Treatment: To clarify the role of NADPH oxidase in the pathophysiology of T cell-initiatedmacrophage-associated allergic asthma, we induced allergen dependent inflammation in a gp91phox-/- SKO (single knockout) and a gp91phox-/- MMP-12-/- DKO (double knockout) mouse and analysed trafficking and functionality of various cell types, the T cell function and T cell-macrophage interaction being given special emphasis.

Results: Composite asthma symptoms expressed in a more aggravated manner in both the KO (SKO and DKO) mice compared to WT indicating that some redundancy may exist in the response pathways of gp91phox and MMP-12. On the one hand, upregulation in macrophage functions such as proliferation, mixed lymphocyte reaction, and MCP-1 directed chemotaxis, may indicate that a regulatory cross-talk is switched on between T cell and macrophage and on the other, downregulation of respiratory burst response hints at a dichotomy in their signaling pathways. Increased B7.1 but reduced B7.2 and MHC class II expression on KO alveolar macrophages may suggest that a switching on-off mechanism is operative where alteration of co-stimulatory molecule expression selectively activating T cell is a critical step.

Inference: T cell mediated functions such as Th2 cytokine secretion, and T cell proliferation in response to OVA were upregulated synchronous with the overall robustness of the asthma phenotype.

Conclusions: As far as cell-cell interaction is concerned, the data is indicative of the existence of a plethora of networks where molecular switches may exist that selectively induce activation and deactivation of regulatory pathways that ultimately manifest in the overall response. gp91phox and MMP-12 either redundantly or synergistically but not additively, provide a regulatory checkpoint for restricting T cell cross-talk with macrophages and keep excessive tissue damage and ECM degradation during acute allergic inflammation under control.

No MeSH data available.


Related in: MedlinePlus

Differential alteration of MHC and co-stimulatory molecules in KO BAL cells. B7.1, B7.2 are co-stimulatory molecules expressed on alveolar macrophages and other antigen presentation cells like the dendritic cells and also B cells and monocytes. Expression of the said molecules were measured by FACS using specific fluorochrome conjugated antibodies from Pharmingen. The data presented shows percent cells positive for the given antigen, expressed as mean ± SEM. n=4/group.
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Figure 9: Differential alteration of MHC and co-stimulatory molecules in KO BAL cells. B7.1, B7.2 are co-stimulatory molecules expressed on alveolar macrophages and other antigen presentation cells like the dendritic cells and also B cells and monocytes. Expression of the said molecules were measured by FACS using specific fluorochrome conjugated antibodies from Pharmingen. The data presented shows percent cells positive for the given antigen, expressed as mean ± SEM. n=4/group.

Mentions: We hypothesized that expression of MHC molecule, which controls T cell activation by APC may be somehow affected in this mechanism. Figure 9 indicates a 1.65-fold increase in post-OVA gp91phox−/− lung parenchyma cells and a 1.38-fold increase in DKO cells in B7.1 positive cells from undetected positive cells in saline treated in any group. B7.2 and MHCII expressions were however decreased in both KO mice with 3.28-fold and 3.18-fold decrease respectively in gp91phox−/− and DKO. MHCII expression was downregulated by 1.18 and 1.13-fold in the two KO mice respectively.


Role of T cells in a gp91phox knockout murine model of acute allergic asthma.

Banerjee ER, Henderson WR - Allergy Asthma Clin Immunol (2013)

Differential alteration of MHC and co-stimulatory molecules in KO BAL cells. B7.1, B7.2 are co-stimulatory molecules expressed on alveolar macrophages and other antigen presentation cells like the dendritic cells and also B cells and monocytes. Expression of the said molecules were measured by FACS using specific fluorochrome conjugated antibodies from Pharmingen. The data presented shows percent cells positive for the given antigen, expressed as mean ± SEM. n=4/group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3643823&req=5

Figure 9: Differential alteration of MHC and co-stimulatory molecules in KO BAL cells. B7.1, B7.2 are co-stimulatory molecules expressed on alveolar macrophages and other antigen presentation cells like the dendritic cells and also B cells and monocytes. Expression of the said molecules were measured by FACS using specific fluorochrome conjugated antibodies from Pharmingen. The data presented shows percent cells positive for the given antigen, expressed as mean ± SEM. n=4/group.
Mentions: We hypothesized that expression of MHC molecule, which controls T cell activation by APC may be somehow affected in this mechanism. Figure 9 indicates a 1.65-fold increase in post-OVA gp91phox−/− lung parenchyma cells and a 1.38-fold increase in DKO cells in B7.1 positive cells from undetected positive cells in saline treated in any group. B7.2 and MHCII expressions were however decreased in both KO mice with 3.28-fold and 3.18-fold decrease respectively in gp91phox−/− and DKO. MHCII expression was downregulated by 1.18 and 1.13-fold in the two KO mice respectively.

Bottom Line: Molecular regulation of inflammation, especially, the role of effector cells in NADPH oxidase-mediated redox reactions for producing O2- (superoxide anion) is a critical step.Materials and Methods and Treatment: To clarify the role of NADPH oxidase in the pathophysiology of T cell-initiatedmacrophage-associated allergic asthma, we induced allergen dependent inflammation in a gp91phox-/- SKO (single knockout) and a gp91phox-/- MMP-12-/- DKO (double knockout) mouse and analysed trafficking and functionality of various cell types, the T cell function and T cell-macrophage interaction being given special emphasis.Composite asthma symptoms expressed in a more aggravated manner in both the KO (SKO and DKO) mice compared to WT indicating that some redundancy may exist in the response pathways of gp91phox and MMP-12.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine, Division of Allergy and Infectious Diseases, Center for Allergy and Inflammation, University of Washington, Room 254, 850 Republican Street, Seattle, WA 98109, USA. enarb1@gmail.com.

ABSTRACT

Objective: Molecular regulation of inflammation, especially, the role of effector cells in NADPH oxidase-mediated redox reactions for producing O2- (superoxide anion) is a critical step. This study explores the roles of macrophages and neutrophils and their cross-talk with extra-cellular matrix components in the light of the role essayed by T cells. Materials and Methods and Treatment: To clarify the role of NADPH oxidase in the pathophysiology of T cell-initiatedmacrophage-associated allergic asthma, we induced allergen dependent inflammation in a gp91phox-/- SKO (single knockout) and a gp91phox-/- MMP-12-/- DKO (double knockout) mouse and analysed trafficking and functionality of various cell types, the T cell function and T cell-macrophage interaction being given special emphasis.

Results: Composite asthma symptoms expressed in a more aggravated manner in both the KO (SKO and DKO) mice compared to WT indicating that some redundancy may exist in the response pathways of gp91phox and MMP-12. On the one hand, upregulation in macrophage functions such as proliferation, mixed lymphocyte reaction, and MCP-1 directed chemotaxis, may indicate that a regulatory cross-talk is switched on between T cell and macrophage and on the other, downregulation of respiratory burst response hints at a dichotomy in their signaling pathways. Increased B7.1 but reduced B7.2 and MHC class II expression on KO alveolar macrophages may suggest that a switching on-off mechanism is operative where alteration of co-stimulatory molecule expression selectively activating T cell is a critical step.

Inference: T cell mediated functions such as Th2 cytokine secretion, and T cell proliferation in response to OVA were upregulated synchronous with the overall robustness of the asthma phenotype.

Conclusions: As far as cell-cell interaction is concerned, the data is indicative of the existence of a plethora of networks where molecular switches may exist that selectively induce activation and deactivation of regulatory pathways that ultimately manifest in the overall response. gp91phox and MMP-12 either redundantly or synergistically but not additively, provide a regulatory checkpoint for restricting T cell cross-talk with macrophages and keep excessive tissue damage and ECM degradation during acute allergic inflammation under control.

No MeSH data available.


Related in: MedlinePlus