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Immunology - Respiratory Medicine

Alveolar Macrophages Play a Key Role in Cockroach-Induced Allergic Inflammation via TNF-a Pathway
Published: Friday, October 19, 2012
Author: Joo Young Kim et al.

by Joo Young Kim, Jung Ho Sohn, Je-Min Choi, Jae-Hyun Lee, Chein-Soo Hong, Joo-Shil Lee, Jung-Won Park

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)-a. We determined whether the serine protease in German cockroach extract (GCE) enhances TNF-a production by alveolar macrophages through the PAR-2 pathway and whether the TNF-a production affects GCE-induced pulmonary inflammation. Effects of GCE on alveolar macrophages and TNF-a 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-a. 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-a production in alveolar macrophages. Blockade of serine proteases prevented the development of GCE induced allergic pathologies. TNF-a blockade also prevented the development of such asthma-like lesions. Depletion of alveolar macrophages reduced AHR and intracellular TNF-a 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-a dependent manner, reflecting the close relation of innate and adaptive immune response in allergic asthma model.