Murine macrophage elastolytic activity induced by Aspergillus fumigatus strains in vitro: evidence of the expression of two macrophage-induced protease genes

The interaction between Aspergillus fumigatus conidia and murine macrophages of various origins was investigated. Cocultures were carried out between A. fumigatus strains and freshly isolated murine pulmonary alveolar macrophages or two murine macrophage cell-lines: murine alveolar cell-line MALU and murine astrocytoma cell-line J774. By measuring the variation of elastolytic activity in the coculture supernatants with two elastin substrates, we demonstrated that either viable or fixed A. fumigatus or C. albicans yeasts or nonspecific particles induced significant macrophage elastolytic activity. The effect of A. fumigatus supernatant or the purified A. fumigatus galactomannan suggested also the possible involvement of this polysaccharide in macrophage-protease gene expression, release, and activity in invasive aspergillosis. The effect of inhibitory compounds demonstrated the potential implication of a macrophagic metalloprotease and a macrophagic cysteine protease. RNA analysis allowed us to demonstrate the induction of expression of two macrophagic protease genes in stimulated macrophages. Two distinctive mechanisms appeared to be implicated in macrophage protease induction: nonspecific phagocytosis in the earliest times of the coculture and (or) specific galactomannan recognition after its gradual release by the mycelium.