Chemoattractant-mediated stimulation of the respiratory burst in human
polymorphonuclear leukocytes may require appearance of protein kinase
activity in the cells' particulate fraction
MC Pike, L Jakoi, LC McPhail and R Snyderman
Low doses of aliphatic alcohols produce divergent effects on the function
of chemoattractant receptors on human polymorphonuclear leukocytes (PMNs)
since they enhance chemotaxis but inhibit stimulation of superoxide
production by chemoattractants. As such, alcohols can provide useful
pharmacologic tools to probe the mechanisms of stimulus- response coupling
in leukocytes. A role for protein kinase C has been implicated in the
activation of the respiratory burst in PMNs. Although the vast majority of
this enzyme activity is located in the cytosolic fraction of unactivated
PMNs, protein kinase C activity appears in the particulate fraction of the
cells when they are stimulated to produce superoxide by either
chemoattractants or by phorbol myristate acetate (PMA). Doses of the
alcohols that selectively inhibited stimulation of superoxide production by
chemoattractants also inhibited the appearance of protein kinase C activity
as well as an undefined protein kinase activity in the particulate fraction
of the cells. In contrast, the alcohols did not affect either the ability
of PMA to stimulate the production of superoxide in PMNs nor the appearance
of protein kinase activity in the cells' particulate fraction. PMA is known
to bind and activate protein kinase C directly, thus bypassing
receptor-mediated events. These data suggest that alcohols inhibit the
stimulation of the respiratory burst by chemoattractants in PMNs by
blocking the ability of receptor occupancy to induce the appearance of
protein kinase activity in particulate fractions. These results moreover
suggest that the appearance of protein kinase activity in the particulate
fraction may be required for activation of the respiratory burst in PMNs.
Volume 67,
Issue 4,
pp. 909-913,
04/01/1986
Copyright © 1986 by The American Society of Hematology