Lysosomal Stability during Phagocytosis of Aspergillus flavus Spores by Alveolar Macrophages of Cortisone-Treated Mice

Abstract

Control mice and those treated with cortisone were exposed to aerosols of viable spores of Aspergillus flavus. Fifteen to 20 minutes later, animals were killed, and alveolar macrophages were obtained by tracheobronchial lavage. Electron-microscopic examination of these cells revealed that, whereas the lysosomes of control macrophages showed extensive attraction and fusion with the phagocytic membranes surrounding spores, the lysosomes of macrophages from animals treated with cortisone revealed little, if any, interaction. This diminished lysosomal response in forming phagocytic vacuoles may be important in the subsequent development of hyphal bronchopneumonia which frequently, occurs in cortisonetreated mice exposed to spores of A. flavus.

Selective Protection against Conidia by Mononuclear and against Mycelia by Polymorphonuclear Phagocytes in Resistance to Aspergillus

“…Our findings extend the observations of Merkow et al (22,28) that macrophages prevented germination of ingested conidia of Aspergillus flavus and that cortisone enhances intracellular germination, not only by duplicating this phenomenon with AF, but also by discovering three new properties of macrophages: (a) they kill ingested spores (Table V), (b) they protect mice even after ablation of PMN (Tables I and II), and (c) their function is impaired by a direct action of cortisone (Table IV).…”

“…In keeping with the reports that inhaled spores of Aspergillus flavus are seen predominantly in phagosomes of alveolar macrophages (22,28) and that spores of AF are selectively phagocytized by mononuclear phagocytes in vitro (10), we found that spores of AF are readily ingested by macrophages in vitro and in vivo and preferentially removed by organs rich in reticuloendothelial phagocytes after i.v. injection.…”

“…Cortisone suppresses the accumulation of phagocytes at inflammatory sites, reduces bactericidal and candidacidal activity of monocytes, and impairs expression of cell-mediated immunity (25)(26)(27). Although none of these actions of cortisone that might affect aspergillosis have been studied systematically, the interesting observation was made that spores of Aspergillus flavus germinated faster in alveolar macrophages of cortisone-treated mice (22,28).…”

Glucocorticoid-Induced Impairment of Macrophage Antimicrobial Activity: Mechanisms and Dependence on the State of Activation

“…Furthermore, dexamethasone treatment of human blood-derived macrophages for 36 h does not affect or only minimally affects the generation of hydrogen peroxide or chemiluminescence in a luminol-or lucigeninamplified system upon stimulation with phorbol myristate acetate (PMA) or opsonized zymosan (authors' unpublished observation). It has been proposed by Merkow et al that lysosomes in macrophages exposed to cortisone do not fuse with phagosomes harboring conidia from Aspergillus [25]. To date we have no evidence in our in vitro model that phagosome-lysosome fusion is disturbed by dexamethasone in cells unable to confine spores ( figure 9).…”

Aspergiloma cerebral

“…(4) obtiveram, tam bém em ratos submetidos à inalação de esporos viáveis de A. flavus,e tratados previam en te com cortisona, quadros gravíssimos de aspergilose cerebral. Nestas condições, a cortisona favorece a infecção, estabilizan do as m em branas das organelas celulares, particularm ente dos lisosomas dos m acró-fagos alveolares, impedindo a liberação das hidrolases ácidas e a destruição do fungo (12,18).…”