Pasteurella haemolytica is a gram negative bacterium frequently isolated from the lungs of calves suffering from a fibrinous pneumonic condition known as shipping fever. To understand the pathogenesis of this disease, we investigated the induction of cytokin gene expression in cultures of bovine alveolar macrophages (BAM) stimulated with heat-killed P. haemolytica. Northern blot analysis of total RNA showed that P. haemolytica induced early, abundant, and consistent synthesis of IL-1, TNF-alpha, and IL-8 mRNA. Cytokine mRNAs were detected within 1 hr post-stimulation with heat-killed P. haemolytica. IL-1 and IL-8 mRNA accumulated to high levels with increase in stimulation time, whereas TNF-alpha mRNA clearly declined by 4 and 8 h post stimulation. IL-1, TNF-alpha, and IL-8 proteins were also secreted into the culture medium of BAM stimulated with heat-killed P. haemolytica. All three proteins were detected at high levels 8 and 12 h post stimulation with P. haemolytica. BAM cells treated with bovine interferon-alpha and then stimulated with P. haemolytica produced higher amounts of IL-1, IL-8 and TNF-alpha proteins compared to BAM stimulated with P. haemolytica alone. These findings demonstrate the powerful and selective induction of cytokine mRNA and protein synthesis in BAM stimulated with heat-killed P. haemolytica and may explain certain aspects of shipping fever pathogenesis.
Copyright 1999 Academic Press.