Main Article Content
Regulation of calcium homeostasis in activated human neutrophils - potential targets for anti-inflammatory therapeutic strategies
Abstract
Design and setting. Laboratory-based experimental research using purified human neutrophils from healthy, adult human volunteers.
Outcome measures. Calcium metabolism and pro-inflammatory activity of neutrophils.
Results. Modulation of calcium fluxes in activated human neutrophils can be achieved by cAMP-dependent upregulation of the activity of the endomembrane Ca2+-ATPase which resequesters cytosolic Ca2+. Formoterol, a long-acting b2-agonist, elevates intracellular cAMP levels, accelerates Ca2+ restoration in activated neutrophils and downregulates the pro-inflammatory responses of these cells. Alterations in the membrane potential of activated neutrophils may play a role in regulating calcium reuptake into the cells as attenuation of the membrane depolarisation response is associated with accelerated calcium influx.
Conclusions. Modulation of the activity of the endomembrane Ca2+-ATPase in human neutrophils represents an important target for anti-inflammatory therapeutic strategies, while new insights into the role played by membrane depolarisation in regulating calcium fluxes in these cells may also facilitate development of novel anti-inflammatory agents directed against neutrophils.
(South African Medical Journal: 2002 92(12): 990-996)