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

Abstract

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-κB 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.

Activation of mast cells by double-stranded RNA: evidence for activation through Toll-like receptor 3

“…Previous reports have shown that dengue virus infection of human MCs stimulates RANTES, macrophage inflammatory protein 1a, and macrophage inflammatory protein 1b, 24 which may recruit inflammatory cells to sites of infection. Still others have shown that rhinovirus infection alone does not alter cytokine production by human basophilic or MC lines 25 but can potentiate IgE-activated IL-4, IL-6, and IL-8 release. 25 These studies suggest that MCs recruit nearby inflammatory cells during a viral infection.…”

“…Still others have shown that rhinovirus infection alone does not alter cytokine production by human basophilic or MC lines 25 but can potentiate IgE-activated IL-4, IL-6, and IL-8 release. 25 These studies suggest that MCs recruit nearby inflammatory cells during a viral infection. Our study suggests that MCs may also activate nearby cells to inhibit viral infection, because IFN-a activates various antiviral pathways 26 and greatly reduces virus replication.…”

Mast cells are permissive for rhinovirus replication: potential implications for asthma exacerbations

“…However, this study was limited to investigating a single RV14 infection titre (10 4 TCID 50 U/mL) of unknown MOI and focused on the modulation of PMA/ionomycin‐ or IgE/anti‐IgE‐dependent histamine and cytokine release 40. Our study has expanded the findings of Hosoda et al .…”

Inflammatory and Bronchospastic Factors in Asthma Exacerbations Caused by Upper Respiratory Tract Infections

“…Influenza virus infection increases basophil LTC 4 release (Huftel et al 1992). Infection of respiratory viruses, including influenza virus and RV, also activates histamine release from peripheral blood basophils (Chonmaitree et al 1988;Huftel et al 1992) and human mast cells (Hosoda et al 2002). Furthermore, RV infection increases bronchial responsiveness to histamine (Gern et al 1997), and histamine content in bronchoalveolar lavage fluid in allergic subjects (Calhoun et al 1994).…”

“…RV infection induces the production of several cytokines such as interleukin (IL)-1 and IL-6 in airway epithelial cells (Terajima et al 1997;Yamaya 2002) and human mast cells (Hosoda et al 2002), and increases IL-6 in nasal washing (Zhu et al 1996). Respiratory virus infections also induce the production of intercellular adhesion molecule-1 (ICAM-1) in the airway epithelial cells (Terajima et al 1997).…”