Cellular protein kinase C activity in asthma.

Protein kinase C (PKC) is a primary group of enzymes mediating signal transduction for a wide variety of functions in many different cell types. Its activation has been implicated in various inflammatory diseases. In asthma, inflammatory cells, such as alveolar macrophages (AM) and polymorphonuclear neutrophils (PMN), are primed and activated compared with those obtained from control subjects. In particular, they release higher amounts of reactive oxygen species. PKC has been known to play an important role in the respiratory burst of human leukocytes. In this study, the PKC activity was measured in blood neutrophils and alveolar macrophages from control (n = 16) and asthmatic subjects (n = 28). In PMN, the total PKC activity was significantly lower in PMN from stable (182.00 +/- 27.20) and unstable (108.40 +/- 14.15) asthmatic patients, compared with control subjects (257.35 +/- 29.70 pmol/10(7) cells/min with p < 0.05 and p < 0.0005, respectively). In AM, PKC activity was 479.50 +/- 71.80 for controls and 254.00 +/- 25.90 pmol/10(7) cells/min for asthmatic patients. Moreover the percentage of membrane PKC was significantly higher in stable asthmatic patients in both cell types. After stimulation of neutrophils with PMA, a significant decrease in total PKC activity was observed in both control and asthmatic subjects. We have found an abnormal regulation of PKC activity in both blood PMNs and AM in asthmatic patients. These findings are consistent with the functional hyperreactivity of inflammatory cells observed in asthma.