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Effects of Rhinovirus Infection on Histamine and Cytokine Production by Cell Lines from Human Mast Cells and Basophils

Masayoshi Hosoda^*, Mutsuo Yamaya^*, Tomoko Suzuki^*, Norihiro Yamada^*, Masato Kamanaka^*, Kiyohisa Sekizawa, Joseph H. Butterfield^¶, Takehiko Watanabe, Hidekazu Nishimura and Hidetada Sasaki^1,*

Departments of ^* Geriatric and Respiratory Medicine and Cellular Pharmacology, Tohoku University School of Medicine, and Virus Center, Clinical Research Division, Sendai National Hospital, Sendai, Japan; Department of Pulmonary Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan; and ^¶ Clinical Research Program in Allergic Diseases, Division of Allergic Diseases and Internal Medicine, Mayo Clinic, Rochester, MN 55905

To understand the biochemical events that occur in the airways after rhinovirus (RV) infection, we developed for the first time a model in which the cell lines from human mast cells (HMC-1) and basophils (KU812) can be infected with RV14, a major group RV. Viral infection was confirmed by demonstrating that viral titers in culture supernatants, and RV RNA increased with time. RV14 infection alone and a combination of PMA plus calcium ionophore A23187, did not increase histamine production by these cells, although IgE plus anti-IgE increased the histamine production. However, histamine content in the supernatants increased in response to PMA plus A23187, or IgE plus anti-IgE after RV14 infection. PMA plus A23187 or IgE plus anti-IgE induced the production of IL-8 and GM-CSF in supernatants of HMC-1 cells and IL-4 and IL-6 in supernatants of KU812 cells. RV14 infection further increased the production of the cytokines, whereas RV14 infection alone did not alter the production of the cytokines by these cells. An Ab to ICAM-1 inhibited RV14 infection of the cells and decreased the production of cytokines and histamine after RV14 infection. RV14 infection enhanced the increases in intracellular calcium concentration and activation of NF-B by PMA plus A23187 in the cells. These findings suggest that RV14 infection may prime the cytokine and histamine production from mast cells and basophils and may cause airway inflammation in asthma.

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