The mononuclear phagocyte system provides a wide based mechanism for defense against invading pathogens. The alveolar macrophage is the major lung component of the mononuclear phagocyte system and has a central regulatory role in defense of the lower respiratory tract against these invading pathogens. Respiratory virus infection remains an important cause of pulmonary inflammation, but the effects of respiratory virus on alveolar macrophage function and regulatory mechanisms have not been defined. In this proposal, we will specifically examine the effects of a common respiratory virus, respiratory syncytial virus (RSV), on human alveolar macrophage which RSV signals altered expression and production of lipid derived mediators and lung cytokines by mononuclear phagocytes (MP). We will specifically examine the mechanism by which respiratory syncytial virus alters mononuclear phagocyte (MP) production of platelet activating factor, and the cytokines IL-1 and TNF which are critical to MP accessory cell function. These studies will be performed on human MP infected in vitro and following in vivo infection. We will further define the effects of the individual surface glycoproteins of RSV (F,G, and SH) expressed in a continuous human pulmonary epithelial cell line following transfection and determine the potency of these gene products to induce alveolar macrophage cytokine and accessory cell function in vitro. These studies will firmly establish the basis for examining domains within these RSV genes capable of altering these MP functions. Together, these studies will define basic mechanisms critically important to virus induced pulmonary inflammation and will directly influence development of potential therapies for this common respiratory virus.
| Panuska, J R; Merolla, R; Rebert, N A et al. (1995) Respiratory syncytial virus induces interleukin-10 by human alveolar macrophages. Suppression of early cytokine production and implications for incomplete immunity. J Clin Invest 96:2445-53 |
| Cirino, N M; Panuska, J R; Villani, A et al. (1993) Restricted replication of respiratory syncytial virus in human alveolar macrophages. J Gen Virol 74 ( Pt 8):1527-37 |
| Panuska, J R; Hertz, M I; Taraf, H et al. (1992) Respiratory syncytial virus infection of alveolar macrophages in adult transplant patients. Am Rev Respir Dis 145:934-9 |
