EFFECTS OF ALKALINE PROTEASE OR RESTRICTOCIN DEFICIENT MUTANTS OF ASPERGILLUS-FUMIGATUS ON HUMAN POLYMORPHONUCLEAR LEUKOCYTES

Several substances including proteases and restrictocin have been sugg ested as candidates for virulence determinants in invasive pulmonary a spergillosis. However, the roles of such substances are not well under stood. This study compared the in vitro suppressive effects of Aspergi llus fumigatus culture filtrates (ACFs), on the functions of human pol ymorphonuclear leukocytes (PMNLs), the principal cells in the host def ence against aspergillus hyphae, from a clinically isolated wild-type and isogenic mutant strains which lack production of elastolytic alkal ine protease (Alp) and/or restrictocin. ACFs were obtained by culturin g conidia of each strain in Medium-199 at 37 degrees C for 5 days. ACF s of the wild-type significantly (p<0.01) suppressed chemotaxis, super oxide anion (O-2(-)) release and PMNL-mediated hyphal damage, compared with the control (Medium-199). ACFs of the mutant strains that lack A lp or restrictocin significantly (p<0.01) suppressed chemotaxis and O- 2(-)-release, but did not suppress hyphal damage, compared with the co ntrol, The wild-type significantly (p<0.01) suppressed chemotaxis of P MNLs compared with the mutant strains lacking Alp or restrictocin, whe reas there were no significant differences in suppression of O-2(-)-re lease and hyphal damage by PMNLs, ACF of a mutant strain that lacks bo th Alp and restrictocin had much less activity, but significantly (p<0 .01) suppressed chemotaxis of PMNLs compared with the control, In conc lusion, alkaline protease and restrictocin may play roles in the suppr essive effect of Aspergillus fumigatus culture filtrates on the functi ons of human polymorphonuclear leukocytes. Other antiphagocytic substa nces produced by Aspergillus fumigatus remain to be identified.