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DUOX-Mediated Signaling Is Not Required for LPS-Induced Neutrophilic Response in the Airways.

Chang S, Linderholm A, Harper R - PLoS ONE (2015)

Bottom Line: We found that LPS induced profound neutrophilic lung inflammation in both Duoxa(+/+)and Duoxa(-/-) mice between 3h and 24h.Duoxa(-/-) mice had significantly higher neutrophil influx 24h after LPS instillation despite similar cytokine levels (KC, MIP-2, or TGF-α) between the two groups.These findings suggest that LPS-TLR-4-induced KC or MIP-2 cytokine induction and subsequent neutrophil recruitment in the airway does not require DUOX-derived hydrogen peroxide from airway epithelium.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, School of Medicine, University of California at Davis, Davis, California 95616, United States.

ABSTRACT
Oxidant production from DUOX1 has been proposed to lead to neutrophil recruitment into the airways when lung homeostasis is compromised. The objective of this study was to determine whether DUOX-derived hydrogen peroxide is required for LPS-induced neutrophil recruitment, using a functional DUOX knock out mouse model. We found that LPS induced profound neutrophilic lung inflammation in both Duoxa(+/+)and Duoxa(-/-) mice between 3h and 24h. Duoxa(-/-) mice had significantly higher neutrophil influx 24h after LPS instillation despite similar cytokine levels (KC, MIP-2, or TGF-α) between the two groups. These findings suggest that LPS-TLR-4-induced KC or MIP-2 cytokine induction and subsequent neutrophil recruitment in the airway does not require DUOX-derived hydrogen peroxide from airway epithelium.

No MeSH data available.


Related in: MedlinePlus

LPS induces predominantly neutrophilic inflammation in both Duoxa-/- and Duoxa+/+ mice.Leukocytes were collected from the airway compartment by BAL at various timepoints up to 7 days (168h) after intratracheal instillation of 1μg LPS. Cell differentials were determined visually based on cell morphology and the percent of neutrophils (A) was compared between Duoxa-/- (-/-) and Duoxa+/+ (+/+) mice. Absolute neutrophil counts (B) were calculated by multiplying neutrophil percentage with total cell number. Data are shown as mean±SEM from six mice in each group; * = p< 0.05 between LPS-treated and PBS-treated controls, # = p<0.05 between LPS-treated Duoxa+/+ and Duoxa-/- mice.
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pone.0131810.g003: LPS induces predominantly neutrophilic inflammation in both Duoxa-/- and Duoxa+/+ mice.Leukocytes were collected from the airway compartment by BAL at various timepoints up to 7 days (168h) after intratracheal instillation of 1μg LPS. Cell differentials were determined visually based on cell morphology and the percent of neutrophils (A) was compared between Duoxa-/- (-/-) and Duoxa+/+ (+/+) mice. Absolute neutrophil counts (B) were calculated by multiplying neutrophil percentage with total cell number. Data are shown as mean±SEM from six mice in each group; * = p< 0.05 between LPS-treated and PBS-treated controls, # = p<0.05 between LPS-treated Duoxa+/+ and Duoxa-/- mice.

Mentions: We analyzed the BALF for macrophages, neutrophils, eosinophils and lymphocytes at 3h, 6h, and 24h after LPS exposure to determine the cell populations recruited by LPS in Duoxa-/- and Duoxa+/+mice. As expected, we observed predominant neutrophilic inflammation in LPS-exposed Duoxa+/+mice (Fig 3A). Surprisingly, Duoxa-/- mice had similar levels of neutrophilic inflammation after LPS exposure (Fig 3A), which conflicts previous reports. Similar to the live cell counts, both Duoxa-/- and Duoxa+/+ mice demonstrated steadily increasing absolute neutrophils counts that peaked at 24h and subsided at 7 days. However, counter to what we would predict a priori, Duoxa-/- mice had a statistically significant increase in neutrophils at the 24h timepoint (Fig 3B).


DUOX-Mediated Signaling Is Not Required for LPS-Induced Neutrophilic Response in the Airways.

Chang S, Linderholm A, Harper R - PLoS ONE (2015)

LPS induces predominantly neutrophilic inflammation in both Duoxa-/- and Duoxa+/+ mice.Leukocytes were collected from the airway compartment by BAL at various timepoints up to 7 days (168h) after intratracheal instillation of 1μg LPS. Cell differentials were determined visually based on cell morphology and the percent of neutrophils (A) was compared between Duoxa-/- (-/-) and Duoxa+/+ (+/+) mice. Absolute neutrophil counts (B) were calculated by multiplying neutrophil percentage with total cell number. Data are shown as mean±SEM from six mice in each group; * = p< 0.05 between LPS-treated and PBS-treated controls, # = p<0.05 between LPS-treated Duoxa+/+ and Duoxa-/- mice.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493023&req=5

pone.0131810.g003: LPS induces predominantly neutrophilic inflammation in both Duoxa-/- and Duoxa+/+ mice.Leukocytes were collected from the airway compartment by BAL at various timepoints up to 7 days (168h) after intratracheal instillation of 1μg LPS. Cell differentials were determined visually based on cell morphology and the percent of neutrophils (A) was compared between Duoxa-/- (-/-) and Duoxa+/+ (+/+) mice. Absolute neutrophil counts (B) were calculated by multiplying neutrophil percentage with total cell number. Data are shown as mean±SEM from six mice in each group; * = p< 0.05 between LPS-treated and PBS-treated controls, # = p<0.05 between LPS-treated Duoxa+/+ and Duoxa-/- mice.
Mentions: We analyzed the BALF for macrophages, neutrophils, eosinophils and lymphocytes at 3h, 6h, and 24h after LPS exposure to determine the cell populations recruited by LPS in Duoxa-/- and Duoxa+/+mice. As expected, we observed predominant neutrophilic inflammation in LPS-exposed Duoxa+/+mice (Fig 3A). Surprisingly, Duoxa-/- mice had similar levels of neutrophilic inflammation after LPS exposure (Fig 3A), which conflicts previous reports. Similar to the live cell counts, both Duoxa-/- and Duoxa+/+ mice demonstrated steadily increasing absolute neutrophils counts that peaked at 24h and subsided at 7 days. However, counter to what we would predict a priori, Duoxa-/- mice had a statistically significant increase in neutrophils at the 24h timepoint (Fig 3B).

Bottom Line: We found that LPS induced profound neutrophilic lung inflammation in both Duoxa(+/+)and Duoxa(-/-) mice between 3h and 24h.Duoxa(-/-) mice had significantly higher neutrophil influx 24h after LPS instillation despite similar cytokine levels (KC, MIP-2, or TGF-α) between the two groups.These findings suggest that LPS-TLR-4-induced KC or MIP-2 cytokine induction and subsequent neutrophil recruitment in the airway does not require DUOX-derived hydrogen peroxide from airway epithelium.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, School of Medicine, University of California at Davis, Davis, California 95616, United States.

ABSTRACT
Oxidant production from DUOX1 has been proposed to lead to neutrophil recruitment into the airways when lung homeostasis is compromised. The objective of this study was to determine whether DUOX-derived hydrogen peroxide is required for LPS-induced neutrophil recruitment, using a functional DUOX knock out mouse model. We found that LPS induced profound neutrophilic lung inflammation in both Duoxa(+/+)and Duoxa(-/-) mice between 3h and 24h. Duoxa(-/-) mice had significantly higher neutrophil influx 24h after LPS instillation despite similar cytokine levels (KC, MIP-2, or TGF-α) between the two groups. These findings suggest that LPS-TLR-4-induced KC or MIP-2 cytokine induction and subsequent neutrophil recruitment in the airway does not require DUOX-derived hydrogen peroxide from airway epithelium.

No MeSH data available.


Related in: MedlinePlus