Am. J. Respir. Cell Mol. Biol., Volume 18, Number 3, March, 1998 435-440

Concentration- and Time-dependent Upregulation and Release of the Cytokines MIP-2, KC, TNF, and MIP-1 in Rat Alveolar Macrophages by Fungal Spores Implicated in Airway Inflammation

Tracy A. Shahan, W. G. Sorenson, Joseph D. Paulauskis, Roger Morey, and Daniel M. Lewis

Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia; and Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts

Inhalation of fungal spores has been shown to cause primary or secondary infection and respiratory inflammation and diseases such as allergic alveolitis, atopic asthma, and organic dust toxic syndrome, which are rarely reported in the absence of predisposing factors. Biochemical and molecular markers of inflammation were measured in rat bronchial alveolar lavage cells (> 95% macrophages) following stimulation with fungal spores isolated from pathogenic and nonpathogenic fungi that have been implicated in airway inflammation. The results of this study demonstrate that mRNA transcripts for the C-X-C branch of the PF4 superfamily are differentially upregulated over those of the C-C mediators in a time- and concentration-dependent manner. Macrophage inflammatory protein (MIP)-2 and KC were differentially upregulated over the acute phase inflammatory cytokines MIP-1 and tumor necrosis factor- (TNF-) in rat alveolar macrophages stimulated with fungal spores from Aspergillus candidus, Aspergillus niger, Eurotium amstelodami, and Cladosporium cladosporioides. Spores from Aspergillus terreus and Penicillium spinulosum failed to stimulate an increase of any cytokine mRNA, whereas those from Aspergillus fumigatus stimulated the upregulation of MIP-2, KC, TNF-, and MIP-1 mRNAs. Over time, A. fumigatus stimulated increasing KC production until 24 h, when production levels increased slightly, then leveled off when measurements ceased at 36 h. Latex spheres stimulated modest amounts of MIP-2 and transforming growth factor- only. These observations suggest that the inflammatory cytokines MIP-2 and KC may be involved in the inflammation arising from the inhalation of fungal spores in a time- and concentration-dependent manner.

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