Abstract
Individuals with heightened airways reactivity, such as asthmatics, may be at risk to inflammatory effects of oxidant air pollutants. In the inbred mouse, significant interstrain variation in airways reactivity to acetylcholine (Ach) and differential susceptibility to ozone (O3)-induced airways inflammation has been described previously. This study used these murine models to test hypotheses that (1) O3-induced hyperreactivity to ACh is a function of inherent baseline ACh reactivity, and (2) susceptibility to O3-induced inflammation is associated with O3-induced hyperreactivity. Strains (15-25 g, 6-8 weeks) with HYPERREACTIVE (DBA/2J, AKR/J, A/J), HYPOREACTIVE (C3H/HeJ, C57BL/6J, SJL/J), or INTERMEDIATE (1291]) phenotypes for ACh reactivity were exposed for 3 h to 2.0 ppm O3 or air (control). ACh reactivity (25 and 50 μg/kg, IV) was assessed 0 and 24 h after exposure. Relative to air controls, mean airways responses to 25 and 50 μg/kg ACh 24 h post-O3 increased significantly in the HYPERREACTIVE AIJ strain (p <.05). Among HYPOREACTIVE strains, O3 significantly (p <.05) increased the response to 50 μg/kg ACh in C57BL/6J and SJL/J strains 24 h postexposure. A/J, C57BL/6J, and SJL/J mice are susceptible to O3-induced lung injury. O3 did not alter ACh reactivity in the other strains. O3 also did not affect airways reactivity to methacholine or carbachol, observations consistent with the hypothesis that O3-induced hyperreactivity to ACh may be due, in part, to O3 effects on cholinesterase function. Treatment of C57BL/6J and AIJ mice with an immunosuppressant (cyclophosphamide) or an anti-PMN antibody significantly (p <.05) attenuated circulating and infiltrating polymorphonuclear leukocytes (PMNs), but did not affect O3-induced hyperreactivity. Therefore, O3-induced ACh hyperreactivity was not a function of baseline reactivity, but correlated with susceptibility to acute O3-induced airways injury and inflammation. Pharmacologic studies suggest that although PMNs were associated with O3-induced hyperreactivity, these cells were not the cause of the effect, and that these two events are not codependent.
| Original language | English |
|---|---|
| Pages (from-to) | 503-518 |
| Number of pages | 16 |
| Journal | Experimental Lung Research |
| Volume | 21 |
| Issue number | 4 |
| DOIs | |
| State | Published - Jan 1 1995 |
| Externally published | Yes |
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Keywords
- Acetylcholine
- Anti-PMN antibody
- Asthma
- Carbachol
- Genetics
- Inflammation
- Methacholine
- PMN
- Polymorphonuclear leukocyte
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Molecular Biology
- Clinical Biochemistry
Cite this
Differential susceptibility to ozone-induced airways hyperreactivity in inbred strains of mice. / Zhang, Liu Yi; Levitt, Roy C; Kleeberger, Steven R.
In: Experimental Lung Research, Vol. 21, No. 4, 01.01.1995, p. 503-518.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Differential susceptibility to ozone-induced airways hyperreactivity in inbred strains of mice
AU - Zhang, Liu Yi
AU - Levitt, Roy C
AU - Kleeberger, Steven R.
PY - 1995/1/1
Y1 - 1995/1/1
N2 - Individuals with heightened airways reactivity, such as asthmatics, may be at risk to inflammatory effects of oxidant air pollutants. In the inbred mouse, significant interstrain variation in airways reactivity to acetylcholine (Ach) and differential susceptibility to ozone (O3)-induced airways inflammation has been described previously. This study used these murine models to test hypotheses that (1) O3-induced hyperreactivity to ACh is a function of inherent baseline ACh reactivity, and (2) susceptibility to O3-induced inflammation is associated with O3-induced hyperreactivity. Strains (15-25 g, 6-8 weeks) with HYPERREACTIVE (DBA/2J, AKR/J, A/J), HYPOREACTIVE (C3H/HeJ, C57BL/6J, SJL/J), or INTERMEDIATE (1291]) phenotypes for ACh reactivity were exposed for 3 h to 2.0 ppm O3 or air (control). ACh reactivity (25 and 50 μg/kg, IV) was assessed 0 and 24 h after exposure. Relative to air controls, mean airways responses to 25 and 50 μg/kg ACh 24 h post-O3 increased significantly in the HYPERREACTIVE AIJ strain (p <.05). Among HYPOREACTIVE strains, O3 significantly (p <.05) increased the response to 50 μg/kg ACh in C57BL/6J and SJL/J strains 24 h postexposure. A/J, C57BL/6J, and SJL/J mice are susceptible to O3-induced lung injury. O3 did not alter ACh reactivity in the other strains. O3 also did not affect airways reactivity to methacholine or carbachol, observations consistent with the hypothesis that O3-induced hyperreactivity to ACh may be due, in part, to O3 effects on cholinesterase function. Treatment of C57BL/6J and AIJ mice with an immunosuppressant (cyclophosphamide) or an anti-PMN antibody significantly (p <.05) attenuated circulating and infiltrating polymorphonuclear leukocytes (PMNs), but did not affect O3-induced hyperreactivity. Therefore, O3-induced ACh hyperreactivity was not a function of baseline reactivity, but correlated with susceptibility to acute O3-induced airways injury and inflammation. Pharmacologic studies suggest that although PMNs were associated with O3-induced hyperreactivity, these cells were not the cause of the effect, and that these two events are not codependent.
AB - Individuals with heightened airways reactivity, such as asthmatics, may be at risk to inflammatory effects of oxidant air pollutants. In the inbred mouse, significant interstrain variation in airways reactivity to acetylcholine (Ach) and differential susceptibility to ozone (O3)-induced airways inflammation has been described previously. This study used these murine models to test hypotheses that (1) O3-induced hyperreactivity to ACh is a function of inherent baseline ACh reactivity, and (2) susceptibility to O3-induced inflammation is associated with O3-induced hyperreactivity. Strains (15-25 g, 6-8 weeks) with HYPERREACTIVE (DBA/2J, AKR/J, A/J), HYPOREACTIVE (C3H/HeJ, C57BL/6J, SJL/J), or INTERMEDIATE (1291]) phenotypes for ACh reactivity were exposed for 3 h to 2.0 ppm O3 or air (control). ACh reactivity (25 and 50 μg/kg, IV) was assessed 0 and 24 h after exposure. Relative to air controls, mean airways responses to 25 and 50 μg/kg ACh 24 h post-O3 increased significantly in the HYPERREACTIVE AIJ strain (p <.05). Among HYPOREACTIVE strains, O3 significantly (p <.05) increased the response to 50 μg/kg ACh in C57BL/6J and SJL/J strains 24 h postexposure. A/J, C57BL/6J, and SJL/J mice are susceptible to O3-induced lung injury. O3 did not alter ACh reactivity in the other strains. O3 also did not affect airways reactivity to methacholine or carbachol, observations consistent with the hypothesis that O3-induced hyperreactivity to ACh may be due, in part, to O3 effects on cholinesterase function. Treatment of C57BL/6J and AIJ mice with an immunosuppressant (cyclophosphamide) or an anti-PMN antibody significantly (p <.05) attenuated circulating and infiltrating polymorphonuclear leukocytes (PMNs), but did not affect O3-induced hyperreactivity. Therefore, O3-induced ACh hyperreactivity was not a function of baseline reactivity, but correlated with susceptibility to acute O3-induced airways injury and inflammation. Pharmacologic studies suggest that although PMNs were associated with O3-induced hyperreactivity, these cells were not the cause of the effect, and that these two events are not codependent.
KW - Acetylcholine
KW - Anti-PMN antibody
KW - Asthma
KW - Carbachol
KW - Genetics
KW - Inflammation
KW - Methacholine
KW - PMN
KW - Polymorphonuclear leukocyte
UR - http://www.scopus.com/inward/record.url?scp=0029156870&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029156870&partnerID=8YFLogxK
U2 - 10.3109/01902149509031755
DO - 10.3109/01902149509031755
M3 - Article
VL - 21
SP - 503
EP - 518
JO - Experimental Lung Research
JF - Experimental Lung Research
SN - 0190-2148
IS - 4
ER -