Am. J. Respir. Crit. Care Med., Vol 155, No. 4, Apr 1997, 1211-1216.
Cellular protein kinase C activity in asthma
I Vachier, P Chanez, T Radeau, C Le Doucen, C Leger and P Godard
Clinique des Maladies Respiratoires, INSERM U 454, Hopital Arnaud de Villeneuve, France.
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.