title: Proteolytic cleavage of the long pentraxin PTX3 in the airways of cystic fibrosis patients.
abstract: The prototypic long pentraxin PTX3, a soluble pattern recognition receptor, plays an important role in innate defense against selected pathogens by favoring their elimination and the initiation of protective responses. PTX3 has notably beneficial effects in mice infected with Aspergillus fumigatus and Pseudomonas aeruginosa. Cystic fibrosis (CF), a severe inherited autosomal recessive disease, is characterized by recurrent lung infections, especially by these two pathogens. We thus hypothesized that the status of PTX3 may be altered in CF patients. Level and integrity of PTX3 were analyzed in the sputum samples from 51 CF patients and 7 patients with chronic obstructive pulmonary disease (COPD). The levels of PTX3 were increased in serums from CF patients, but low in their respiratory secretions. PTX3 concentrations in sputum samples were dramatically lower in CF patients than in COPD patients. The low concentration of PTX3 resulted from a proteolysis cleavage by elastase and A. fumigatus proteases. Interestingly, the N-ter domain of PTX3, involved in protection against A. fumigatus, is preferentially degraded by these proteases. These results indicate that the selective proteolysis of PTX3 in the CF lung may explain, in part, the recurrent lung infections by PTX3-sensitive pathogens in CF patients.
authors.affiliation: 1LUNAM Université, Université d'Angers, Angers, France.
authors.forename: Yveline
authors.initials: Y
authors.lastname: Hamon
authors.forename: Sébastien
authors.initials: S
authors.lastname: Jaillon
authors.forename: Christine
authors.initials: C
authors.lastname: Person
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Giniès
authors.forename: Erwan
authors.initials: E
authors.lastname: Garo
authors.forename: Barbara
authors.initials: B
authors.lastname: Bottazzi
authors.forename: Sarah
authors.initials: S
authors.lastname: Ghamrawi
authors.forename: Thierry
authors.initials: T
authors.lastname: Urban
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Subra
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Bouchara
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
authors.forename: Pascale
authors.initials: P
authors.lastname: Jeannin
authors.forename: Yves
authors.initials: Y
authors.lastname: Delneste
mesh_terms: D000293:Adolescent; D000328:Adult; D001232:Aspergillus fumigatus / Q000276:immunology*; D001426:Bacterial Proteins / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism*; D002648:Child; D003550:Cystic Fibrosis / Q000150:complications / Q000276:immunology*; D005260:Female; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D008297:Male; D009894:Opportunistic Infections / Q000150:complications / Q000276:immunology*; D010196:Pancreatic Elastase / Q000378:metabolism; D059748:Proteolysis; D011552:Pseudomonas Infections / Q000150:complications / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D055732:Pulmonary Aspergillosis / Q000150:complications / Q000276:immunology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000276:immunology*; D020545:Respiratory Mucosa / Q000276:immunology* / Q000382:microbiology; D000683:Serum Amyloid P-Component / Q000378:metabolism*; D013183:Sputum / Q000378:metabolism*; D055815:Young Adult; D000099153:Pentraxins
chemical_list: D001426:Bacterial Proteins; D001798:Blood Proteins; D002097:C-Reactive Protein; D010196:Pancreatic Elastase; D000683:Serum Amyloid P-Component; D000099153:Pentraxins
keywords: Aspergillus fumigatus; cystic fibrosis; elastase; pentraxin 3