Bovine parainfluenza-3 virus selectively depletes a calcium-independent, phospholipid-dependent protein kinase C and inhibits superoxide anion generation in bovine alveolar macrophages.
Bovine parainfluenza-3 (PI-3) virus inhibits oxygen-dependent bacterial killing by phagocytes, a key pulmonary defense, thus predisposing the host to intrapulmonary bacterial superinfection. PI-3 virus inhibited opsonized zymosan or PMA-activated superoxide anion (O2-) generation in bovine alveolar macrophages. The respiratory virus influenza also inhibits O2- generation by phagocytes, however, the mechanisms(s) of viral inhibition differs from PI-3. PI-3 did not trigger O2- generation before inhibition, whereas influenza triggered O2- generation before desensitization of ligand-initiated respiratory burst. PI-3 modified the twin signals of calcium and protein kinase C in alveolar macrophages. PI-3 infection increased macrophage membrane permeability to extracellular calcium, but did not inhibit calcium mobilization triggered by opsonized zymosan. These effects further distinguish bovine PI-3 from human influenza, which triggers mobilization of cell-associated calcium and inhibits calcium mobilization activated by physiologic ligands. Macrophages possessed two classes of PKC activity, a calcium/phosphatidylserine/diglyceride (Ca/PS/DG))-dependent activity and a Ca-independent, PS/DG-dependent histone IIIS phosphorylating activity. PI-3 infection selectively depleted the Ca-independent, PS/DG-dependent kinase activity but not the classical Ca/PS/DG-dependent activity. Inhibition of Ca-independent, PS/DG-dependent kinase activity and inhibition of O2- generation by PI-3 occurred at a similar viral dose and time frame, suggesting a role for this kinase in activating the respiratory burst. Inhibition of the oxygen-dependent bactericidal function of alveolar macrophages and disturbances in signal transduction may contribute to the immunosuppression and bacterial superinfection accompanying viral respiratory disease.
Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104-4399.
R M
RM
Dyer
S
S
Majumdar
S D
SD
Douglas
H M
HM
Korchak
D000818:Animals; D002417:Cattle; D003600:Cytosol / Q000378:metabolism; D066298:In Vitro Techniques; D015759:Ionomycin / Q000494:pharmacology; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000276:immunology*; D010224:Parainfluenza Virus 3, Human / Q000276:immunology* / Q000472:pathogenicity; D011493:Protein Kinase C / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D013481:Superoxides; D015759:Ionomycin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate