Mechanisms of chronic ozone exposure: Role of mast cells

Steven R. Kleeberger, Malinda Longphre, Clarke Tankersley, Yoshinori Ohtsuka

Research output: Contribution to journalArticle

Abstract

Background: Acute exposure to ozone (O3) induces lung inflammation and hyperpermeability, and causes epithelial injury of upper (nasal) and lower airways. Mast cells are important regulatory cells for each of these effects. Chronic (prolonged) O3 exposures cause epithelial injury and interstitial fibrosis in terminal bronchi and proximal alveoli, but little is known about mechanisms of injury. As acute inflammation may be linked to the pathogenesis of many airways diseases, we hypothesized that airway susceptibility to prolonged O3 exposure is mediated, in part, by mast cells. Approach: Regional airways responses to prolonged O3 exposure were assessed in genetically mast cell-deficient mice (WBB6F1-W/Wv). Their responses were compared to those in normal, mast cell sufficient, congenic littermates (WBB6F1-+/+), and W/Wv mice that were repleted of mast cells by bone marrow transplantation from +/+ donors (BMT-W/Wv). Following acclimation to exposure chambers with filtered air only, animals from each treatment group (N = 4/group) were exposed to 0.30 ppm O3 (profile pattern) 8 h/d, 5 d/wk for 14 d, 30 d, 90 d, and 90 d with 35 d recovery in HEPA-filtered air. Between 8 h exposures, mice were exposed continuously to 0.06 ppm O3. Age-matched mice were simultaneously exposed to filtered air (0.0 ppm O3) to serve as O3 controls. Mice were assessed for regional airway inflammation and permeability [bronchoalveolar (BAL) and nasal (NL) lavage], epithelial proliferation, and changes in airway morphometry. Results: Mean numbers of macrophages and epithelial cells recovered by BAL after 14-90 days O3 increased significantly (p <0.05) in each strain relative to age- and strainmatched mice exposed to filtered air. Further, the numbers of BAL cells from +/+ and BMT-W/Wv mice were significantly greater than those from W/Wv animals, but were not different from each other. After 35 d recovery, the numbers of BAL macrophages and epithelial cells were not different between O3- and air-treatment groups. There were no significant effects of strain, exposure, or time on BAL neutrophils or lymphocytes. BAL protein (a marker of lung permeability) and DNA synthesis in the centriacinar epithelium (i.e. cell proliferation) were increased significantly in O3-exposed +/+ and BMT-W/Wv, but not W/Wv mice, compared to air controls. The effect on protein was reversed after 35 d recovery. Epithelial proliferation remained significantly elevated or increased in +/+ and BMT-W/Wv mice after O3 exposure. Changes in wall thickness of small airways were determined by image analysis and planimetry. Results largely paralleled those of estimates of epithelial proliferation. Nasal responses to prolonged O3 were also evaluated in these groups of mice. There were no significant O3-induced increases in lavageable cells or protein in any of the strains, nor was there significant change in epithelial proliferation, relative to air controls. Conclusions: Results of these experiments are consistent with the hypothesis that mast cells significantly affect the pathogenesis of bronchiolar epithelial injury and proliferation induced by prolonged exposure to an environmentally relevant concentration of O3. Inasmuch as mast cell densities are increased in airways of allergic asthmatics, this may have important implications in understanding why asthmatics are more susceptible to inhaled pollutants. Funding: Health Effects Institute.

Original languageEnglish (US)
Pages (from-to)381-382
Number of pages2
JournalZentralblatt fur Hygiene und Umweltmedizin
Volume200
Issue number4
StatePublished - 1997

Fingerprint

Ozone
Mast Cells
Air
Wounds and Injuries
Nose
Permeability
Cell Count
Epithelial Cells
Macrophages
Nasal Lavage
Inflammation
Proteins
Acclimatization
Bronchoalveolar Lavage
Bronchi
Bone Marrow Transplantation
Pneumonia
Neutrophils
Fibrosis
Epithelium

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health

Cite this

Kleeberger, S. R., Longphre, M., Tankersley, C., & Ohtsuka, Y. (1997). Mechanisms of chronic ozone exposure: Role of mast cells. Zentralblatt fur Hygiene und Umweltmedizin, 200(4), 381-382.

Mechanisms of chronic ozone exposure : Role of mast cells. / Kleeberger, Steven R.; Longphre, Malinda; Tankersley, Clarke; Ohtsuka, Yoshinori.

In: Zentralblatt fur Hygiene und Umweltmedizin, Vol. 200, No. 4, 1997, p. 381-382.

Research output: Contribution to journalArticle

Kleeberger, SR, Longphre, M, Tankersley, C & Ohtsuka, Y 1997, 'Mechanisms of chronic ozone exposure: Role of mast cells', Zentralblatt fur Hygiene und Umweltmedizin, vol. 200, no. 4, pp. 381-382.
Kleeberger SR, Longphre M, Tankersley C, Ohtsuka Y. Mechanisms of chronic ozone exposure: Role of mast cells. Zentralblatt fur Hygiene und Umweltmedizin. 1997;200(4):381-382.
Kleeberger, Steven R. ; Longphre, Malinda ; Tankersley, Clarke ; Ohtsuka, Yoshinori. / Mechanisms of chronic ozone exposure : Role of mast cells. In: Zentralblatt fur Hygiene und Umweltmedizin. 1997 ; Vol. 200, No. 4. pp. 381-382.
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TY - JOUR

T1 - Mechanisms of chronic ozone exposure

T2 - Role of mast cells

AU - Kleeberger, Steven R.

AU - Longphre, Malinda

AU - Tankersley, Clarke

AU - Ohtsuka, Yoshinori

PY - 1997

Y1 - 1997

N2 - Background: Acute exposure to ozone (O3) induces lung inflammation and hyperpermeability, and causes epithelial injury of upper (nasal) and lower airways. Mast cells are important regulatory cells for each of these effects. Chronic (prolonged) O3 exposures cause epithelial injury and interstitial fibrosis in terminal bronchi and proximal alveoli, but little is known about mechanisms of injury. As acute inflammation may be linked to the pathogenesis of many airways diseases, we hypothesized that airway susceptibility to prolonged O3 exposure is mediated, in part, by mast cells. Approach: Regional airways responses to prolonged O3 exposure were assessed in genetically mast cell-deficient mice (WBB6F1-W/Wv). Their responses were compared to those in normal, mast cell sufficient, congenic littermates (WBB6F1-+/+), and W/Wv mice that were repleted of mast cells by bone marrow transplantation from +/+ donors (BMT-W/Wv). Following acclimation to exposure chambers with filtered air only, animals from each treatment group (N = 4/group) were exposed to 0.30 ppm O3 (profile pattern) 8 h/d, 5 d/wk for 14 d, 30 d, 90 d, and 90 d with 35 d recovery in HEPA-filtered air. Between 8 h exposures, mice were exposed continuously to 0.06 ppm O3. Age-matched mice were simultaneously exposed to filtered air (0.0 ppm O3) to serve as O3 controls. Mice were assessed for regional airway inflammation and permeability [bronchoalveolar (BAL) and nasal (NL) lavage], epithelial proliferation, and changes in airway morphometry. Results: Mean numbers of macrophages and epithelial cells recovered by BAL after 14-90 days O3 increased significantly (p <0.05) in each strain relative to age- and strainmatched mice exposed to filtered air. Further, the numbers of BAL cells from +/+ and BMT-W/Wv mice were significantly greater than those from W/Wv animals, but were not different from each other. After 35 d recovery, the numbers of BAL macrophages and epithelial cells were not different between O3- and air-treatment groups. There were no significant effects of strain, exposure, or time on BAL neutrophils or lymphocytes. BAL protein (a marker of lung permeability) and DNA synthesis in the centriacinar epithelium (i.e. cell proliferation) were increased significantly in O3-exposed +/+ and BMT-W/Wv, but not W/Wv mice, compared to air controls. The effect on protein was reversed after 35 d recovery. Epithelial proliferation remained significantly elevated or increased in +/+ and BMT-W/Wv mice after O3 exposure. Changes in wall thickness of small airways were determined by image analysis and planimetry. Results largely paralleled those of estimates of epithelial proliferation. Nasal responses to prolonged O3 were also evaluated in these groups of mice. There were no significant O3-induced increases in lavageable cells or protein in any of the strains, nor was there significant change in epithelial proliferation, relative to air controls. Conclusions: Results of these experiments are consistent with the hypothesis that mast cells significantly affect the pathogenesis of bronchiolar epithelial injury and proliferation induced by prolonged exposure to an environmentally relevant concentration of O3. Inasmuch as mast cell densities are increased in airways of allergic asthmatics, this may have important implications in understanding why asthmatics are more susceptible to inhaled pollutants. Funding: Health Effects Institute.

AB - Background: Acute exposure to ozone (O3) induces lung inflammation and hyperpermeability, and causes epithelial injury of upper (nasal) and lower airways. Mast cells are important regulatory cells for each of these effects. Chronic (prolonged) O3 exposures cause epithelial injury and interstitial fibrosis in terminal bronchi and proximal alveoli, but little is known about mechanisms of injury. As acute inflammation may be linked to the pathogenesis of many airways diseases, we hypothesized that airway susceptibility to prolonged O3 exposure is mediated, in part, by mast cells. Approach: Regional airways responses to prolonged O3 exposure were assessed in genetically mast cell-deficient mice (WBB6F1-W/Wv). Their responses were compared to those in normal, mast cell sufficient, congenic littermates (WBB6F1-+/+), and W/Wv mice that were repleted of mast cells by bone marrow transplantation from +/+ donors (BMT-W/Wv). Following acclimation to exposure chambers with filtered air only, animals from each treatment group (N = 4/group) were exposed to 0.30 ppm O3 (profile pattern) 8 h/d, 5 d/wk for 14 d, 30 d, 90 d, and 90 d with 35 d recovery in HEPA-filtered air. Between 8 h exposures, mice were exposed continuously to 0.06 ppm O3. Age-matched mice were simultaneously exposed to filtered air (0.0 ppm O3) to serve as O3 controls. Mice were assessed for regional airway inflammation and permeability [bronchoalveolar (BAL) and nasal (NL) lavage], epithelial proliferation, and changes in airway morphometry. Results: Mean numbers of macrophages and epithelial cells recovered by BAL after 14-90 days O3 increased significantly (p <0.05) in each strain relative to age- and strainmatched mice exposed to filtered air. Further, the numbers of BAL cells from +/+ and BMT-W/Wv mice were significantly greater than those from W/Wv animals, but were not different from each other. After 35 d recovery, the numbers of BAL macrophages and epithelial cells were not different between O3- and air-treatment groups. There were no significant effects of strain, exposure, or time on BAL neutrophils or lymphocytes. BAL protein (a marker of lung permeability) and DNA synthesis in the centriacinar epithelium (i.e. cell proliferation) were increased significantly in O3-exposed +/+ and BMT-W/Wv, but not W/Wv mice, compared to air controls. The effect on protein was reversed after 35 d recovery. Epithelial proliferation remained significantly elevated or increased in +/+ and BMT-W/Wv mice after O3 exposure. Changes in wall thickness of small airways were determined by image analysis and planimetry. Results largely paralleled those of estimates of epithelial proliferation. Nasal responses to prolonged O3 were also evaluated in these groups of mice. There were no significant O3-induced increases in lavageable cells or protein in any of the strains, nor was there significant change in epithelial proliferation, relative to air controls. Conclusions: Results of these experiments are consistent with the hypothesis that mast cells significantly affect the pathogenesis of bronchiolar epithelial injury and proliferation induced by prolonged exposure to an environmentally relevant concentration of O3. Inasmuch as mast cell densities are increased in airways of allergic asthmatics, this may have important implications in understanding why asthmatics are more susceptible to inhaled pollutants. Funding: Health Effects Institute.

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