Effects of concurrent ozone exposure on the pathogenesis of cigarette smoke-induced emphysema in B6C3F1 mice

被引:28
作者
March, TH [1 ]
Barr, EB [1 ]
Finch, GL [1 ]
Nikula, KJ [1 ]
Seagrave, JC [1 ]
机构
[1] Lovelace Resp Res Inst, Albuquerque, NM 87108 USA
关键词
D O I
10.1080/08958370290084818
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Episodic elevation of air pollutants may exacerbate respiratory distress associated with chronic obstructive pulmonary disease (COPD), yet few experiments have been performed to determine how continuously polluted atmospheres may contribute to the etiology of COPD, in general and pulmonary emphysema in particular. This study describes the effects of concurrent exposure to ozone (0,) in the pathogenesis of cigarette smoke (CS)-induced emphysema in the mouse. Female B6C3F(1) mice were whole-body exposed either to filtered air (FA) or to mainstream CS at a concentration of 250 mg total particulate material/m(3) for 6 h/day, 5 days/wk for 15 or 32 wk. Concurrently, mice were exposed either to FA or to O-3 at 0.3 ppm for 8 h/night, 5 nights/wk for the same time periods. At necropsy, mouse lungs were lavaged, and bronchoalveolar lavage fluid (BALF) was analyzed for inflammatory cell numbers, total protein, lactate dehydrogenase (LDH) and alkaline phosphatase (AP) activities, superoxide production by isolated alveolar macrophages, glutathione content, inflammatory cytokines, and proteolytic activity. Other lungs were inflated at constant pressure for 6 h with formalin for fixation, routine histopathology, and stereology. After 32 wk of exposure, CS with or without concurrent 0, exposure produced stereologic evidence of emphysema as previously described. Concurrent O-3. exposure did not worsen any of these parameters, nor did O-3 by itself cause stereologic changes that were consistent with emphysema. The O-3 exposure caused only slight elevations of BALE macrophages, while CS exposure caused marked increases in the numbers of both BALE macrophages and neutrophils. Neutrophils in the BALF in response to CS exposure were also more numerous at 32 wk than at 15 wk. Exposure to CS caused an increase in BALE total protein, LDH, AP, and interleukin (IL)-1beta. After 32 wk, CS exposure was associated with decreased superoxide production from isolated alveolar macrophages. The CS exposure elevated BALE total glutathione primarily at 15 wk. Overall, O-3 had little effect on endpoints that were significantly affected by CS exposure. We conclude that concurrent O-3 exposure has no effect on the induction of emphysema by CS in this animal model.
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页码:1187 / 1213
页数:27
相关论文
共 63 条
[21]   EFFECT OF CHRONIC CIGARETTE-SMOKE EXPOSURE ON LUNG CLEARANCE OF TRACER PARTICLES INHALED BY RATS [J].
FINCH, GL ;
NIKULA, KJ ;
CHEN, BT ;
BARR, EB ;
CHANG, IY ;
HOBBS, CH .
FUNDAMENTAL AND APPLIED TOXICOLOGY, 1995, 24 (01) :76-85
[22]   Chronic cigarette smoke exposure increases the pulmonary retention and radiation dose of 239Pu inhaled as 239PuO2 by F344 rats [J].
Finch, GL ;
Lundgren, DL ;
Barr, EB ;
Chen, BT ;
Griffith, WC ;
Hobbs, CH ;
Hoover, MD ;
Nikula, KJ ;
Mauderly, JL .
HEALTH PHYSICS, 1998, 75 (06) :597-609
[23]   ALVEOLAR INFLAMMATION AND ITS RELATION TO EMPHYSEMA IN SMOKERS [J].
FINKELSTEIN, R ;
FRASER, RS ;
GHEZZO, H ;
COSIO, MG .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1995, 152 (05) :1666-1672
[24]   Matrix metalloproteinase expression and production by alveolar macrophages in emphysema [J].
Finlay, GA ;
ODriscoll, LR ;
Russell, KJ ;
DArcy, EM ;
Masterson, JB ;
Fitzgerald, MX ;
OConnor, CM .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1997, 156 (01) :240-247
[25]   THE PROTEASE-ANTIPROTEASE BALANCE WITHIN THE HUMAN LUNG - IMPLICATIONS FOR THE PATHOGENESIS OF EMPHYSEMA [J].
GADEK, JE ;
PACHT, ER .
LUNG, 1990, 168 :552-564
[26]  
GREEN F H Y, 1992, American Review of Respiratory Disease, V145, pA321
[27]  
Harkema JR, 1997, MICROSC RES TECHNIQ, V36, P276, DOI 10.1002/(SICI)1097-0029(19970215)36:4<276::AID-JEMT5>3.0.CO
[28]  
2-K
[29]   Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice [J].
Hautamaki, RD ;
Kobayashi, DK ;
Senior, RM ;
Shapiro, SD .
SCIENCE, 1997, 277 (5334) :2002-2004
[30]   INACTIVATION OF ALPHA-1-ANTITRYPSIN BY AQUEOUS COAL SOLUTIONS - POSSIBLE RELATION TO THE EMPHYSEMA OF COAL-WORKERS [J].
HUANG, X ;
LAURENT, PA ;
ZALMA, R ;
PEZERAT, H .
CHEMICAL RESEARCH IN TOXICOLOGY, 1993, 6 (04) :452-458