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Effect of ozone exposure and infection on bronchoalveolar lavage: sex differences in response patterns.

ABSTRACT: Female mice exhibit a better survival rate than males after infection, but if infection follows an ozone-induced oxidative stress, male survival exceeds that of females. Our goal was to study bronchoalveolar lavage factors that contribute to these sex differences in outcome. We studied parameters at 4, 24, and 48 h after ozone exposure and infection, including markers of inflammation, oxidative stress, and tissue damage, and surfactant phospholipids and surfactant protein A (SP-A). A multianalyte immunoassay at the 4h time point measured 59 different cytokines, chemokines, and other proteins. We found that: (1) Although some parameters studied revealed sex differences, no sex differences were observed in LDH, total protein, MIP-2, and SP-A. Males showed more intragroup significant differences in SP-A between filtered air- and ozone-exposed mice compared to females. (2) Oxidized dimeric SP-A was higher in FA-exposed female mice. (3) Surfactant phospholipids were typically higher in males. (4) The multianalyte data revealed differences in the exuberance of responses under different conditions - males in response to infection and females in response to oxidative stress. These more exuberant, and presumably less well-controlled responses associate with the poorer survival. We postulate that the collective effects of these sex differences in response patterns of lung immune cells may contribute to the clinical outcomes previously observed.

SUBMITTER: Mikerov AN

PROVIDER: S-EPMC4169765 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Effect of ozone exposure and infection on bronchoalveolar lavage: sex differences in response patterns.

Mikerov Anatoly N AN Phelps David S DS Gan Xiaozhuang X Umstead Todd M TM Haque Rizwanul R Wang Guirong G Floros Joanna J

Toxicology letters 20140421 2

Female mice exhibit a better survival rate than males after infection, but if infection follows an ozone-induced oxidative stress, male survival exceeds that of females. Our goal was to study bronchoalveolar lavage factors that contribute to these sex differences in outcome. We studied parameters at 4, 24, and 48 h after ozone exposure and infection, including markers of inflammation, oxidative stress, and tissue damage, and surfactant phospholipids and surfactant protein A (SP-A). A multianalyt ...[more]

PMID: 24769259

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Project description:BackgroundOzone is a major component of air pollution. Exposure to this powerful oxidizing agent can cause or exacerbate many lung conditions, especially those involving innate immunity. Surfactant protein-A (SP-A) plays many roles in innate immunity by participating directly in host defense as it exerts opsonin function, or indirectly via its ability to regulate alveolar macrophages and other innate immune cells. The mechanism(s) responsible for ozone-induced pathophysiology, while likely related to oxidative stress, are not well understood.MethodsWe employed 2-dimensional difference gel electrophoresis (2D-DIGE), a discovery proteomics approach, coupled with MALDI-ToF/ToF to compare the bronchoalveolar lavage (BAL) proteomes in wild type (WT) and SP-A knockout (KO) mice and to assess the impact of ozone or filtered air on the expression of BAL proteins. Using the PANTHER database and the published literature most identified proteins were placed into three functional groups.ResultsWe identified 66 proteins and focused our analysis on these proteins. Many of them fell into three categories: defense and immunity; redox regulation; and protein metabolism, modification and chaperones. In response to the oxidative stress of acute ozone exposure (2 ppm; 3 hours) there were many significant changes in levels of expression of proteins in these groups. Most of the proteins in the redox group were decreased, the proteins involved in protein metabolism increased, and roughly equal numbers of increases and decreases were seen in the defense and immunity group. Responses between WT and KO mice were similar in many respects. However, the percent change was consistently greater in the KO mice and there were more changes that achieved statistical significance in the KO mice, with levels of expression in filtered air-exposed KO mice being closer to ozone-exposed WT mice than to filtered air-exposed WT mice.ConclusionWe postulate that SP-A plays a role in reactive oxidant scavenging in WT mice and that its absence in the KO mice in the presence or absence of ozone exposure results in more pronounced, and presumably chronic, oxidative stress.

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Effect of ozone exposure and infection on bronchoalveolar lavage: sex differences in response patterns.

Publications

Effect of ozone exposure and infection on bronchoalveolar lavage: sex differences in response patterns.

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