Effects of alkaline protease or restrictocin deficient mutants of Aspergillus fumigatus on human polymorphonuclear leukocytes

Several substances including proteases and restrictocin have been suggested as candidates for virulence determinants in invasive pulmonary aspergillosis. However, the roles of such substances are not well understood. This study compared the in vitro suppressive effects of Aspergillus fumigatus culture filtrates (ACFs), on the functions of human polymorphonuclear leukocytes (PMNLs), the principal cells in the host defence against aspergillus hyphae, from a clinically isolated wild-type and isogenic mutant strains which lack production of elastolytic alkaline protease (Alp) and/or restrictocin. ACFs were obtained by culturing conidia of each strain in Medium- 199 at 37 degrees C for 5 days. ACFs of the wild-type significantly (p<0.01) suppressed chemotaxis, superoxide anion (O2-) release and PMNL-mediated hyphal damage, compared with the control (Medium-199). ACFs of the mutant strains that lack Alp or restrictocin significantly (p<0.01) suppressed chemotaxis and O2(-)-release, but did not suppress hyphal damage, compared with the control. The wild-type significantly (p<0.01) suppressed chemotaxis of PMNLs compared with the mutant strains lacking Alp or restrictocin, whereas there were no significant differences in suppression of O2(-)-release and hyphal damage by PMNLs. ACF of a mutant strain that lacks both Alp and restrictocin had much less activity, but significantly (p<0.01) suppressed chemotaxis of PMNLs compared with the control. In conclusion, alkaline protease and restrictocin may play roles in the suppressive effect of Aspergillus fumigatus culture filtrates on the functions of human polymorphonuclear leukocytes. Other antiphagocytic substances produced by Aspergillus fumigatus remain to be identified.

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