Differential Rac activation by major and minor group rhinovirus results in altered MAPK activation and cytokine release from human macrophages

Abstract

Viral respiratory infections are a major cause of asthma exacerbations and can contribute to the pathogenesis of asthma. Major‐ and minor‐group human rhinoviruses (HRV) enter cells by binding to the cell surface molecules ICAM‐1 and LDL‐R that are present on epithelial cells and macrophages. The focus of the resulting viral infection is in bronchial epithelia. Despite this, previous studies of HRV infection and subsequent cytokine dysregulation have implicated macrophages as playing a role in establishing the inflammatory environment seen in HRV infection and asthma exacerbation. We demonstrate that the small molecular‐weight G‐protein Rac is differentially activated by the binding of major‐ and minor‐group rhinovirus to macrophages, that MCP‐1 release differs between the two viruses, and that inhibition of Rac attenuates the activation of the stress kinase p38 and the release of MCP‐1. Interestingly, RANTES release is not affected by Rac inhibition. This is the first report of a relationship involving major‐ or minor‐group HRV exposure, small molecular‐weight G‐protein activation, MCP‐1 release and macrophages, suggesting that Rac plays a role in establishing the inflammatory microenvironment initiated in the human airway upon exposure to rhinovirus. This work was supported by the Wriston scholarship, NIH R15 AI065505‐01A1 and NSF 0521112.