IONIZING-RADIATION INCREASES ENDOTHELIAL AND EPITHELIAL-CELL PRODUCTION OF INFLUENZA-VIRUS AND LEUKOCYTE ADHERENCE

To characterize the effect of (CO)-C-60 gamma radiation on cell-cell a nd pathogen-cell interactions, the adherence of undifferentiated HL-60 cells to HUVEC monolayers was tested in the absence and presence of L PS or influenza virus type A. Basal HL-60 cell adherence to uninfected HUVEC monolayers (3.0 +/- 1.6%, n = 30) was not altered when HUVECs w ere exposed to 1- to 10-Gy gamma irradiation 4 to 72 h before the adhe sion assay. LPS treatment of HUVEC monolayers (0.5 mu g/ml, 4 h) produ ced a 6.9-fold increase in adherence that was not altered by previous irradiation. However, when HUVEC monolayers were subjected to 1-10 Gy 41 h before influenza virus infection (10(6) pfu/ml) for 7 h, virus-in duced adherence was enhanced in a dose-dependent manner. Increased vir us hemagglutinin (HA) protein expression mediated the radiation-induce d adherence for the following reasons: 1) HA Ag increases paralleled i ncreases in leukocyte adherence. 2) Northern blot analysis demonstrate d a time-dependent increase in mRNA HA levels. 3) Anti-HA blocked HL-6 0 cell adherence to irradiated and virus-infected HUVEC monolayers. Th ese changes were associated with an increased virus titer yield and vi rus-induced HUVEC killing. In contrast, cytotoxicity produced by vesic ular stomatitis virus, which unlike influenza virus replicates cytopla smically, was not altered by radiation in HUVECs. In related studies, the canine kidney epithelial (MDCK) cell line showed a similar increas ed influenza virus production after gamma radiation, indicating that t he radiation-induced increase in production of influenza virus is not cell-specific and probably involves a nuclear mechanism.