Inflammation, mucous cell metaplasia, and Bcl-2 expression in response to inhaled lipopolysaccharide aerosol and effect of rolipram

Journal Article · Wed Jun 15 00:00:00 EDT 2011 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2011.04.001· OSTI ID:21587768

Smith, Kevin R; Leonard, David; McDonald, Jacob D; Tesfaigzi, Yohannes

Our previous studies have characterized the inflammatory response of intratracheally instilled lipopolysaccharides (LPS) in F344/N rats. To better reflect the environmentally relevant form of LPS exposure, the present study evaluated the inflammatory response of F344/N rats exposed to LPS by inhalation. Rats were exposed by nose-only inhalation to aerosolized LPS at a median particle diameter of 1 {mu}m and a dose range from 0.08 to 480 {mu}g. Animals were euthanized 72 h post exposure and the inflammatory cell counts and differentials, the cytokine/chemokine levels in the bronchoalveolar lavage fluid (BALF), and the changes in intraepithelial stored mucosubstances, mucous cells per mm basal lamina, and Bcl-2-positive mucous cells were quantified. We observed a dose-dependent increase reaching maximum values at the 75 {mu}g LPS dose for the numbers of neutrophils, macrophages and lymphocytes, for the levels of IL-6, IL-1{alpha}, IL-1{beta}, TNF{alpha}, MCP-1 and GRO-KC. In addition, mucous cell metaplasia and the percentage of Bcl-2-positive mucous cells were increased with an increasing deposited LPS dose. When rats were treated with the phosphodiesterase-4 (PDE4) inhibitor, rolipram (10 mg/kg), prior to exposure to aerosolized LPS neutrophil numbers in the BAL were reduced at 8 h but not at 24 or 72 h post LPS exposure. These results demonstrate that exposure to aerosolized LPS resulted in a more potent inflammatory response at lower doses and that inflammation was more uniformly distributed throughout the lung compared to inflammation caused by intratracheal LPS instillation. Therefore, this animal model will be useful for screening efficacy of anti-inflammatory drugs.

• OSTI ID: 21587768
• Journal Information: Toxicology and Applied Pharmacology, Vol. 253, Issue 3; Other Information: DOI: 10.1016/j.taap.2011.04.001; PII: S0041-008X(11)00128-1; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AEROSOLS
APOPTOSIS
DOSES
DRUGS
INFLAMMATION
INHALATION
LIPOPOLYSACCHARIDES
LUNGS
LYMPHOCYTES
NEUTROPHILS
PHOSPHODIESTERASES
RATS
ANIMAL CELLS
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CARBOHYDRATES
COLLOIDS
CONNECTIVE TISSUE CELLS
DISPERSIONS
ENZYMES
ESTERASES
HYDROLASES
INTAKE
LEUKOCYTES
LIPIDS
MAMMALS
MATERIALS
ORGANIC COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
POLYSACCHARIDES
PROTEINS
RESPIRATORY SYSTEM
RODENTS
SACCHARIDES
SOLS
SOMATIC CELLS
SYMPTOMS
VERTEBRATES