Effect of bovine parainfluenza-3 virus on bovine pulmonary macrophages: Inhibition of the respiratory burst and alterations in calcium and protein kinase C signaling
Phagocyte dysfunction during bovine Parainfluenza-3 virus (PI-3) infection promotes the overgrowth of Pasteurella hemolytica in the bovine lung. Therefore, killing functions were evaluated in the normal and PI-3 exposed bovine alveolar macrophage, a pivotal defense structure of the lung. Macrophages generated superoxide anion, a critical component for microbicidal activity, when stimulated with opsonized zymosan or phorbol myristate acetate. PI-3 inhibited superoxide anion production in cells activated by either stimulant. The virus neither triggered superoxide anion generation nor depressed macrophage viability. Calcium and protein kinase C transduce activation signals for superoxide anion generation. In bovine macrophages, opsonized zymosan stimulated a prompt increase in cytosolic calcium. The increases in calcium were necessary but insufficient to trigger superoxide anion generation. Phorbol esters triggered superoxide anion generation without effects on cytosolic calcium indicating protein kinase C circumvented the calcium-dependent signals. Protein kinase C is a family of kinase isotypes with calcium, phosphatidylserine/diacylglycerol dependent or phosphatidylserine/diacylglycerol but calcium independent kinase activity. This study demonstrated that bovine macrophages contained both the calcium-dependent and the calcium-independent protein kinase C activities. PI-3 altered the protein kinase C and the calcium-dependent signaling mechanisms for superoxide anion generation. The virus triggered increases in cytosolic calcium that originated from extracellular calcium. Nevertheless, opsonized zymosan triggered normal increases in calcium in PI-3 exposed macrophages. PI-3 also selectively depleted the calcium-independent protein kinase C activity. These findings indicated PI-3 inhibited superoxide anion generation in association with plasma membrane permeabilization to extracellular calcium and depletion of protein kinase activity. PI-3 might suppress phagocytic cell function by the modulation of intracellular mechanisms of signal transduction.
Animal diseases|Cellular biology|Veterinary services
Dyer, Robert Moorehead, "Effect of bovine parainfluenza-3 virus on bovine pulmonary macrophages: Inhibition of the respiratory burst and alterations in calcium and protein kinase C signaling" (1991). Dissertations available from ProQuest. AAI9211930.