Author of

• 11503

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  P2.03 - Poster Session 2 - Technology and Novel Development (ID 151)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11510

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    P2.03-007 - Changes in pulmonary immune cell recruitment and function during cigarette smoke-induced lung carcinogenesis in mice (ID 3370)

    09:30 - 09:30  |  Author(s): M. Johnson
    • Abstract

    Background
    Smoking-mediated lung cancer will cause at least 134,000 deaths in the USA this year. Even when detected at the earliest stages (stage IA and IB), five year survival is just slightly more than 50%. Chronic pulmonary inflammation is an established risk factor for lung cancer. Increased lung tumor macrophage infiltration is associated with poor prognosis, and murine lung tumor models exhibit increased macrophage infiltration. We hypothesize that chronic cigarette smoke exposure causes changes in inflammatory cell numbers and phenotypes creating a permissive environment for tumor formation. Chemopreventive agents such as the prostacyclin analog iloprost, may mitigate these changes.

    Methods
    FVB mice were given control AIN-76A chow or AIN-76A with 0.015% pioglitazone two weeks prior to smoke exposure. Mice were exposed to 70-90 mg/m[3] particulate level cigarette smoke for 6 hours/day, 5 days/week. Lungs were harvested 1 and 22 weeks after smoke exposure and after 22 weeks smoke/20 weeks ambient air (standard protocol for tumor induction). Bronchoalveolar cells were collected for qRT-PCR analysis of macrophage markers. Tumors were harvested and dissected from uninvolved tissue. Uninvolved lung tissue was digested and immune cell content analyzed by flow cytometry.

    Results
    Cigarette smoke exposure induced changes in macrophage phenotype after 1 week as indicated by CD11b exression (flow cytometry) and phenotypic markers (qRT-PCR). Macrophage infiltration increased in 22 week smoke/20 week ambient air exposed mice. Neutrophil numbers were increased at one week of smoke exposure. CD4 and CD8 positive T cell numbers decreased during smoke exposure but returned to control levels after smoking cessation. Smoke exposure differentially affected macrophage programming at each time point.

    Conclusion
    Cigarette smoke exposure affects pulmonary inflammatory cell numbers and function as early as 1 week after smoking initiation. Some of these changes are transient (increases in neutrophil numbers), while others are consistent but return to normal after smoking cessation (decreases in T cell populations). Smoke exposure resulted in early functional effects on macrophages and alveolar macrophage infiltration was still increased 20 weeks after smoking cessation, indicating that the effects of cigarette smoking on innate immunity are long lasting.