STIMULATION OR INHIBITION OF THE RESPIRATORY BURST IN CULTURED MACROPHAGES IN A MYCOBACTERIUM MODEL - INITIAL STIMULATION IS FOLLOWED BY INHIBITION AFTER PHAGOCYTOSIS

Microorganisms cause varying degrees of stimulation of superoxide (O-2 (-)) production (respiratory burst [RB]) in macrophages but in some ca ses apparently inhibit the RB induced in the same monolayers by a conv entional stimulator. We have explored these differences. A mycobacteri um model, the slowly multiplying mouse pathogen Mycobacterium microti, induced a modest RB in resident macrophage monolayers, compared with the substantial RB induced by opsonized zymosan (Zy). However, if the 1-h M. microti pulse immediately preceded the Zy assay (instead of bei ng concurrent), the RB was consistently less than that elicited by the Zy alone. Cytochalasin (an inhibitor of phagocytosis) enhanced Zy-ind uced RB, supporting the view that the burst is cell surface mediated, but his agent apparently eliminated the inhibition of the Zy-induced R B caused by prior M. microti exposure, suggesting that this inhibition may have an intracellular origin. The inhibition described extended n ot only to another mycobacterium (Mycobacterium bovis BCG) but also to a previous application of Zy itself. The general implications for mac rophage functions of these observations on timing and sites of initiat ion are briefly discussed.