title: Chitinases in Pneumocystis carinii pneumonia.
abstract: Pneumocystis pneumonia remains an important complication of immune suppression. The cell wall of Pneumocystis has been demonstrated to potently stimulate host inflammatory responses, with most studies focusing on β-glucan components of the Pneumocystis cell wall. In the current study, we have elaborated the potential role of chitins and chitinases in Pneumocystis pneumonia. We demonstrated differential host mammalian chitinase expression during Pneumocystis pneumonia. We further characterized a chitin synthase gene in Pneumocystis carinii termed Pcchs5, a gene with considerable homolog to the fungal chitin biosynthesis protein Chs5. We also observed the impact of chitinase digestion on Pneumocystis-induced host inflammatory responses by measuring TNFα release and mammalian chitinase expression by cultured lung epithelial and macrophage cells stimulated with Pneumocystis cell wall isolates in the presence and absence of exogenous chitinase digestion. These findings provide evidence supporting a chitin biosynthetic pathway in Pneumocystis organisms and that chitinases modulate inflammatory responses in lung cells. We further demonstrate lung expression of chitinase molecules during Pneumocystis pneumonia.
authors.affiliation: Department of Internal Medicine, Thoracic Diseases Research Unit, Division of Pulmonary and Critical Care, Mayo Clinic, 8-24 Stabile Building, Rochester, MN 55905, USA.
authors.forename: Leah R
authors.initials: LR
authors.lastname: Villegas
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Kottom
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Limper
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002473:Cell Wall / Q000201:enzymology; D002478:Cells, Cultured; D002686:Chitin / Q000378:metabolism*; D002687:Chitin Synthase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002688:Chitinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000201:enzymology; D005260:Female; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000201:enzymology*; D008264:Macrophages / Q000201:enzymology / Q000276:immunology; D008969:Molecular Sequence Data; D045363:Pneumocystis carinii / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity*; D011020:Pneumonia, Pneumocystis / Q000382:microbiology / Q000503:physiopathology*; D051381:Rats; D017422:Sequence Analysis, DNA; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D005656:Fungal Proteins; D014409:Tumor Necrosis Factor-alpha; D002686:Chitin; D002687:Chitin Synthase; D002688:Chitinases