HUMAN AND RAT MACROPHAGES MEDIATE FUNGISTATIC ACTIVITY AGAINST RHIZOPUS SPECIES DIFFERENTLY - IN-VITRO AND EX-VIVO STUDIES

Both rat alveolar macrophages and a human macrophage cell line with ch aracteristics of human tissue (e.g., alveolar) macrophages (THP-1) wer e found to inhibit the germination of Rhizopus spores. However, the co nditions under which fungistatic activity occurs are different for the se two cell types. The inhibition of Rhizopus spore germination by rat alveolar macrophages requires the activation of macrophages and the p resence of serum and L-arginine. During rat alveolar macrophage-mediat ed fungistatic activity, L-arginine is oxidized to nitrite. Human macr ophage-mediated fungistatic activity is similar to that mediated by ra t macrophages in terms of the serum requirement, but it does not requi re L-arginine. Human macrophages did not produce any nitrite detectabl e by the colorimetric assay. Their ability to inhibit germination was enhanced by the combination of endotoxin and gamma interferon. The inh ibition of Rhizopus spore germination by rat alveolar macrophages is t hus mediated by the generation of nitric oxide, whereas the mechanism of similar inhibition by human macrophages remains poorly understood. Serum samples from diabetic rats as well as from patients with diabete s or uremia decreased the inhibitory effect of macrophages on spore ge rmination. Dialysis of the serum samples against a buffered salt solut ion antagonized this phenomenon, indicating that a low-molecular-weigh t factor in the sera of patients with diabetes or uremia may modulate local antifungal defense mechanisms, The absence of L-arginine-depende nt nitrogen oxidation in human macrophages, compared with its presence in rat alveolar macrophages, under conditions during which fungistati c activity occurs suggests that this phenomenon is species specific.