Platelet-activating factor induces a concentration-dependent spectrum of functional responses in bovine neutrophils

We characterized the dose response of bovine neutrophils to platelet-activa ting factor (PAF) with respect to the following functions: calcium flux and membrane potential changes, actin polymerization, degranulation, and the p roduction and/or priming of the oxidative burst, PAF at very low concentrat ions (10(-10) and 10(-9) M) caused changes in intracellular calcium and mem brane potential in bovine neutrophils, whereas moderate PAF concentrations (greater than or equal to 10(-7) M) resulted in increased actin polymerizat ion. Degranulation responses to PAF were more complex: low concentrations ( 10(-9) M) caused secretory ganule degranulation, moderate doses (greater th an or equal to 10(-7) M) caused specific granule degranulation, whereas azu rophil degranulation only occurred at high (10(-5) M) PAF concentrations, T reatment of bovine neutrophils with PAF at concentrations greater than or e qual to 10(-7) M also caused up-regulation of the adhesion molecules Mac-1 and L-selectin, PAF stimulation resulted in a very weak [compared to phorbo l myristate acetate (PMA)] oxidative burst in bovine neutrophils, and only at high (10(-6) M) concentrations, Unlike human neutrophils, bovine neutrop hils were poorly primed by PAF treatment, Only high concentrations of PAF ( 10(-5) M) caused an increased rate of PMA-stimulated superoxide production, although lower doses of PAF did reduce the lag time preceding the PMA-indu ced oxidative burst, The overall pattern that can be inferred is that lower concentrations of PAF promote neutrophil sensitivity and interaction by se lective degranulation, up-regulation of adhesion molecules, and increased a ctin polymerization. In contrast, higher PAF concentrations can promote, al beit weakly, more direct bactericidal responses, such as the release of rea ctive oxygen species and granule enzymes, The ability of PAF to modulate a graded response in bovine neutrophils would allow the cell to respond propo rtionally to the severity of a stimulus.