Exposure to Aspergillus fumigatus spores induces chemokine expression in mouse macrophages.
Inhalation of fungal spores may cause inflammation and respiratory diseases, such as bronchitis, allergic alveolitis, and asthma. Alveolar macrophages provide the first line of defense in the respiratory tract. To examine the cellular mechanisms involved in Aspergillus fumigatus-induced airway inflammation, mouse macrophage cell line (RAW 264.7) cells were exposed for 2 h or 6 h to graded doses of A. fumigatus spores that were either alive or heat-killed. Furthermore, the ability of the cells to phagocytize the spores was visualized by electron microscopy. Expression of selected cytokines and chemokines was assessed by a real time quantitative PCR method and by enzyme-linked immunoabsorbent assay (ELISA) after exposure. A significant increase in mRNA expression of TNF-alpha, MIP-1alpha, MIP-1beta, and MCP-1 was observed with a maximal induction at 6h after exposure to the highest (1 x 10(7)) concentration of live spores. Similar response was not detected with heat-killed spores in the expression of chemokines and cytokines, even though there were no differences between the phagocytosis of live and heat-killed spores. These results suggest that exposure to live spores of A. fumigatus can modulate the expression of proinflammatory cytokines and chemokines in mouse macrophages and thus influence the development of inflammatory processes in the airways.
Pylkkänen
Lea
L
Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, Helsinki.
Gullstén
Harriet
H
Majuri
Marja-Leena
ML
Andersson
Ulpu
U
Vanhala
Esa
E
Määttä
Juha
J
Meklin
Teija
T
Hirvonen
Maija-Riitta
MR
Alenius
Harri
H
Savolainen
Kai
K
D000818:Animals; D001232:Aspergillus fumigatus; D002460:Cell Line; D018932:Chemokine CCL2 / Q000096:biosynthesis; D018925:Chemokines / Q000096:biosynthesis*; D016207:Cytokines / Q000096:biosynthesis; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D015850:Interleukin-6 / Q000096:biosynthesis; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008854:Microscopy, Electron; D010587:Phagocytosis / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013172:Spores, Fungal; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D018932:Chemokine CCL2; D018925:Chemokines; D016207:Cytokines; D018076:DNA, Complementary; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha