EFFECTS OF CONCANAVALIN-A ON NA-DEPENDENT AND NA+-INDEPENDENT MECHANISMS FOR H+ EXTRUSION IN ALVEOLAR MACROPHAGES()

Alveolar macrophages (m phi) possess two parallel mechanisms for plasm alemmal H+ extrusion: a V-type H+ pump (V-ATPase) and a Na+/H+ exchang er (NHE). To investigate the coordinated functioning of these H+ extru ders for m phi intracellular pH (pH(i)) regulation, we investigated th e effects of the plant lectin concanavalin A (ConA) on resident alveol ar m phi from rabbits. ConA (1 mu M, 30-min pretreatment) activated th e m phi for phagocytosis of opsonized Escherichia coli. ConA activatio n did not affect the baseline pH(i) of m phi or the initial rate of pH (i) recovery (dpH(i)/dt) from an intracellular acid load (acid-loaded pH(i) nadir approximate to 6.9). However, the contributions of Naf-ind ependent H+ transport (i.e. V-ATPase activity) and Nac-dependent H+ tr ansport (i.e. NHE activity) to dpH(i)/dt were altered significantly. T he lectin stimulated Na+/H+ exchange and inhibited V-ATPase activity. In control m phi, V-ATPase-mediated H+ extrusion was responsible for > 80% of dpH(i)/dt. Conversely, in ConA-treated m phi, Na+/H+ exchange w as responsible for similar to 65% of dpH(i)/dt, and V-ATPase activity was responsible for only 35% of dpH(i)/dt. These results underscore th e complex mechanisms and signaling pathways that coordinate the activi ties of cellular acid-base transporters in m phi pH(i) regulation.