Effects of Concanavalin A on Na+-Dependent and Na+-Independent Mechanisms for H+ Extrusion in Alveolar Macrophages
Alveolar macrophages (mφ) possess two parallel mechanisms for plasmalemmal H+ extrusion: a V-type H+ pump (V-ATPase) and a Na+/H+ exchanger (NHE). To investigate the coordinated functioning of these H+ extruders for mφ intracellular pH (pHi) regulation, we investigated the effects of the plant lectin concanavalin A (ConA) on resident alveolar mφ from rabbits. ConA (1 μM, 30-min pretreatment) activated the mφ for phagocytosis of opsonized Escherichia coli. ConA activation did not affect the baseline pHi of mφ or the initial rate of pHi recovery (dpHi/dt) from an intracellular acid load (acid-loaded pHi nadir ≈ 6.9). However, the contributions of Na+-independent H+ transport (i.e. V-ATPase activity) and Na+-dependent H+ transport (i.e. NHE activity) to dpHi/dt were altered significantly. The lectin stimulated Na+/H+ exchange and inhibited V-ATPase activity. In control mφ, V-ATPase-mediated H+ extrusion was responsible for >80% of dpHi/dt. Conversely, in ConA-treated mφ, Na+/H+ exchange was responsible for ∼65% of dpHi/dt, and V-ATPase activity was responsible for only 35% of dpHi/dt. These results underscore the complex mechanisms and signaling pathways that coordinate the activities of cellular acid-base transporters in mφ pHi regulation.
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