Relation of Cytosolic Calcium to the Microbicidal Activation of Blood Monocytes by Recombinant Interferon

Abstract
Oxygen metabolism and calcium ion (Ca++) handling in blood monocytes were greatly affected by treatment with recombinant γ interferon (rIFN-γ). Incubating the monocytes with rIFN-γ resulted in increased basal production of superoxide anion, as well as a significantly enhanced respiratory burst in response to concanavalin A (Con A). A concomitant increase in microbicidal activity against Listeria monocytogenes was observed, and cell membrane permeability to Ca++ was enhanced by treatment with rIFN-γ. Con A stimulation was also associated with acute rises in cytosolic-free calcium, and these calcium transients were greatly augmented in cells pretreated with rIFN-γ. The enhanced respiratory burst and the increased calcium transients were completely neutralized by a monoclonal antibody to rIFN-γ. Furthermore, enhancement of the respiratory burst and calcium transients occurred in a parallel dose-response range for rIFN-γ. Blocking the intracellular release of calcium into cytosol by TMB-8 abrogated the capacity of rIFN-γ to enhance the monocyte respiratory burst. Thus, not only was rIFN-γ treatment of monocytes associated with altered calcium metabolism, but calcium from intracellular pools was essential to the expression of this activated state during Con A stimulation.

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