Ionizing radiation increases endothelial and epithelial cell production of influenza virus and leukocyte adherence

To characterize the effect of 60Co gamma radiation on cell-cell and pathogen-cell interactions, the adherence of undifferentiated HL-60 cells to HUVEC monolayers was tested in the absence and presence of LPS 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 were exposed to 1- to 10-Gy gamma irradiation 4 to 72 h before the adhesion assay. LPS treatment of HUVEC monolayers (0.5 microgram/ml, 4 h) produced 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-induced adherence was enhanced in a dose-dependent manner. Increased virus hemagglutinin (HA) protein expression mediated the radiation-induced adherence for the following reasons: 1) HA Ag increases paralleled increases in leukocyte adherence. 2) Northern blot analysis demonstrated a time-dependent increase in mRNA HA levels. 3) Anti-HA blocked HL-60 cell adherence to irradiated and virus-infected HUVEC monolayers. These changes were associated with an increased virus titer yield and virus-induced HUVEC killing. In contrast, cytotoxicity produced by vesicular stomatitis virus, which unlike influenza virus replicates cytoplasmically, was not altered by radiation in HUVECs. In related studies, the canine kidney epithelial (MDCK) cell line showed a similar increased influenza virus production after gamma radiation, indicating that the radiation-induced increase in production of influenza virus is not cell-specific and probably involves a nuclear mechanism.