Suppressive effects of Aspergillus fumigatus culture filtrates on human alveolar macrophages and polymorphonuclear leucocytes

Aspergillus spp., especially A. fumigatus (Af) can colonize the airways and the lungs with localized underlying conditions and further invade the surrounding lung tissues, even in subjects without systemic predisposing factors, presumably by escaping the local host defences. To clarify the mechanisms of colonization and invasion of Af, we investigated the in vitro effects of Af culture filtrates (ACFs) on the functions of human alveolar macrophages (AMs), and polymorphonuclear leucocytes (PMNs). ACFs were obtained by culturing clinically isolated AF in Medium-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 incubation period in Medium-199. However, the percentage decreased 24% when incubated with a final concentration of 30% ACF in Medium-199. With respect to the antichemotactic activity on human PMNs, 3% ACF was sufficient for significant suppression, and 30% ACF completely inhibited the migration of PMNs. In addition, phorbol myristate acetate (PMA)-induced O-2(-) release from PMNs was significantly suppressed in Medium-199 which included 12.5% ACF or more. The antichemotactic activity of ACF was partially abolished by trypsin or chicken egg ovomacroglobulin. When ACF was separated into two fractions (molecular weight >10 and <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 the colonization of Af in the bronchopulmonary tissues and allow this species to invade surrounding lung tissues in pulmonary aspergillosis by suppressing local host defences.