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Alveolar Macrophages Play a Key Role in Cockroach-Induced Allergic Inflammation via TNF-? Pathway.
PLoS One. 2012;7(10):e47971
Authors: Kim JY, Sohn JH, Choi JM, Lee JH, Hong CS, Lee JS, Park JW
Abstract
The activity of the serine protease in the German cockroach allergen is important to the development of allergic disease. The protease-activated receptor (PAR)-2, which is expressed in numerous cell types in lung tissue, is known to mediate the cellular events caused by inhaled serine protease. Alveolar macrophages express PAR-2 and produce considerable amounts of tumor necrosis factor (TNF)-?. We determined whether the serine protease in German cockroach extract (GCE) enhances TNF-? production by alveolar macrophages through the PAR-2 pathway and whether the TNF-? production affects GCE-induced pulmonary inflammation. Effects of GCE on alveolar macrophages and TNF-? production were evaluated using in vitro MH-S and RAW264.6 cells and in vivo GCE-induced asthma models of BALB/c mice. GCE contained a large amount of serine protease. In the MH-S and RAW264.7 cells, GCE activated PAR-2 and thereby produced TNF-?. In the GCE-induced asthma model, intranasal administration of GCE increased airway hyperresponsiveness (AHR), inflammatory cell infiltration, productions of serum immunoglobulin E, interleukin (IL)-5, IL-13 and TNF-? production in alveolar macrophages. Blockade of serine proteases prevented the development of GCE induced allergic pathologies. TNF-? blockade also prevented the development of such asthma-like lesions. Depletion of alveolar macrophages reduced AHR and intracellular TNF-? level in pulmonary cell populations in the GCE-induced asthma model. These results suggest that serine protease from GCE affects asthma through an alveolar macrophage and TNF-? dependent manner, reflecting the close relation of innate and adaptive immune response in allergic asthma model.
PMID: 23094102 [PubMed – in process]
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