SUPPRESSIVE EFFECTS OF ASPERGILLUS-FUMIGATUS CULTURE FILTRATES ON HUMAN ALVEOLAR MACROPHAGES AND POLYMORPHONUCLEAR LEUKOCYTES

Aspergillus spp., especially A. fumigatus (Af) can colonize the airway s and the lungs with localized underlying conditions and further invad e the surrounding lung tissues, even in subjects without systemic pred isposing factors, presumably by escaping the local host defences. To c larify the mechanisms of colonization and invasion of Af, we investiga ted the in vitro effects of Af culture filtrates (ACFs) on the functio ns of human alveolar macrophages (AMs), and polymorphonuclear leucocyt es (PMNs). ACFs were obtained by culturing clinically isolated AF in M edium-199 at 37 degrees C for 5 days. In the study of phagocytosis of Af conidia by human AMs, 52% of AMs ingested conidia during a 60 min i ncubation period in Medium-199. However, the percentage decreased 24% when incubated with a final concentration of 30% ACF in Medium-199. Wi th respect to the antichemotactic activity on human PMNs, 3% ACF was s ufficient for significant suppression, and 30% ACF completely inhibite d the migration of PMNs. In addition, phorbol myristate acetate (PMA)- induced O-2(-) release from PMNs was significantly suppressed in Mediu m-199 which included 12.5% ACF or more. The antichemotactic activity o f ACF was partially abolished by trypsin or chicken egg ovomacroglobul in. When ACF was separated into two fractions (molecular weight >10 an d <10 kDa) by dialysis and centrifugation through CL-LGC filters, both fractions retained the antichemotactic activity. We conclude that Af produce several antiphagocytic factors, which can be responsible for t he colonization of Af in the bronchopulmonary tissues and allow this s pecies to invade surrounding lung tissues in pulmonary aspergillosis b y suppressing local host defences.