title: Activation of platelets by Aspergillus fumigatus and potential role of platelets in the immunopathogenesis of Aspergillosis.
abstract: Aspergillus fumigatus is the most frequent cause of invasive mold infections worldwide. Platelets contribute to inflammation and promote thrombosis, characteristically seen in aspergillosis, and might be involved both in antifungal defense and in the histopathological process. In the experiments reported here, in vitro activation of platelets by conidia, swollen conidia, and hyphae from A. fumigatus was assessed by flow cytometry and enzyme immunoassays. THP-1 monocytes and human monocytes with and without platelets were cultured with hyphae from A. fumigatus, and the release of interleukin-8 (IL-8) was measured by enzyme immunoassays. A. fumigatus potently induced the expression of CD62-p and CD63 and the release of CD40 ligand, RANTES, and Dickkopf homolog 1 in platelets, with particularly enhancing effects of hyphae compared with conidia. The hypha-mediated activation of platelets further enhanced the release of IL-8 both in THP-1 monocytes and in human adherent monocytes. In conclusion, we have found that A. fumigatus is a potent inducer of platelet-mediated inflammation, potentially promoting protective as well as harmful responses during aspergillosis.
authors.affiliation: Research Institute for Internal Medicine, Rikshospitalet, N-0027, Oslo, Norway. kristian.rodland@rr-research.no
authors.forename: Ernst Kristian
authors.initials: EK
authors.lastname: Rødland
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.forename: Turid M
authors.initials: TM
authors.lastname: Pedersen
authors.forename: Bente
authors.initials: B
authors.lastname: Halvorsen
authors.forename: Fredrik
authors.initials: F
authors.lastname: Muller
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.forename: Stig S
authors.initials: SS
authors.lastname: Frøland
mesh_terms: D015703:Antigens, CD; D001228:Aspergillosis / Q000382:microbiology* / Q000473:pathology*; D001232:Aspergillus fumigatus / Q000472:pathogenicity*; D001792:Blood Platelets / Q000382:microbiology*; D002460:Cell Line; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D025301:Hyphae / Q000472:pathogenicity; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D009000:Monocytes / Q000737:chemistry / Q000382:microbiology; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D013172:Spores, Fungal / Q000472:pathogenicity; D060149:Tetraspanin 30
chemical_list: D015703:Antigens, CD; C554586:CD63 protein, human; D018946:Chemokine CCL5; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30