ADMINISTRATION OF ANTIGRANULOCYTE MAB RB6-8C5 IMPAIRS THE RESISTANCE OF MICE TO LISTERIA-MONOCYTOGENES INFECTION

Mice injected i.p. with RB6-8C5 mAb experienced a profound depletion o f neutrophils in the bloodstream and spleen and significant impairment of their resistance to experimental infection with Listeria monocytog enes. Control mice survived i.v. inoculation with 5 X 10(4) L. monocyt ogenes; whereas, most RB6-8C5 mAb-treated mice inoculated i.v. with as few as 10 L. monocytogenes died within 6 days. RB6-8C5 mAb treatment was particularly deleterious when given within the first 24 h after i. v. inoculation with L. monocytogenes; however, some adverse effect was observed even when administration was delayed until 3 or 5 days after bacterial inoculation. Histopathologic examination of the livers of R B6-8C5 mAb-treated mice revealed necrotic foci that were characterized by few inflammatory cells and massive numbers of Gram-positive bacter ia within hepatocytes. Additional evidence that the effects of RB6-8C5 mAb administration were chiefly due to neutrophil depletion include: 1) the effects of RB6-8C5 mAb treatment occurred more rapidly than wha t is generally seen in mice treated with anti-T cell mAbs, 2) similar results were observed with normal and scid mice, 3) RB6-8C5 mAb admini stration did not diminish delayed-type hypersensitivity nor the abilit y of spleen cells from immunized mice to transfer resistance, and 4) n atural killer cell activity was unaffected by RB6-8C5 mAb administrati on. The results of this study provide additional evidence in support o f the importance of neutrophils in the early stage of innate resistanc e to murine listeriosis.