title: Assessment of epithelial innate antimicrobial factors in sinus tissue from patients with and without chronic rhinosinusitis.
abstract: BACKGROUND
  Airway secretions contain endogenous antimicrobial factors (AMFs) that contribute to the innate host defense of the respiratory tract. Antibacterial peptides as well as host-derived lipids including cholesteryl esters have been detected in maxillary lavage fluid. Sterol O-acyltransferase 1 (SOAT1) is a key enzyme in cholesteryl ester production. The purpose of this study is to determine if such intrinsic microbicidal molecules are acutely expressed within sinus tissue and to compare levels of expression between patients with and without chronic rhinosinusitis (CRS).
  
  
  METHODS
  Sinus tissue was obtained from subjects with (24) and without (9) a history of CRS. Six CRS patients had nasal polyposis (CRSwNP). Immunofluorescence staining for human neutrophil peptide (HNP) was done as a marker for inflammation. Real-time polymerase chain reaction (RT-PCR) following RNA extraction was used to quantify the expression of SOAT-1, the epithelial beta-defensins (HBD2 and HBD3), and the cathelicidin LL37 with ribosomal protein, large, P0 (RPLP0) as the housekeeping gene.
  
  
  RESULTS
  Immunofluorescence showed significant increase in HNP staining in CRS patients without nasal polyposis (CRSsNP) vs non-CRS specimens (p = 0.010), in agreement with clinical inflammation status. SOAT1 messenger RNA (mRNA) expression was also upregulated in CRSsNP compared to non-CRS (p = 0.041) and CRSwNP (p = 0.005) patients, whereas increases for HBD2 and HBD3 were less prominent. LL37 was either absent or expressed at very low levels in all samples.
  
  
  CONCLUSIONS
  Increased biosynthesis of SOAT1, a key enzyme for antimicrobial cholesteryl ester production, was observed in the sinus tissue of CRSsNP patients but not in CRSwNP patients. This further supports the novel concept of lipid-mediated innate mucosal defense and delineates CRS with and without nasal polyposis as distinct subtypes.
authors.affiliation: Orange County Sinus Institute, Southern California Permanente Medical Group (SCPMG), Irvine, CA; Department of Otolaryngology-Head and Neck Surgery, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA.
authors.forename: Jivianne T
authors.initials: JT
authors.lastname: Lee
authors.forename: Oswaldo H
authors.initials: OH
authors.lastname: Escobar
authors.forename: Rabin
authors.initials: R
authors.lastname: Anouseyan
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Janisiewicz
authors.forename: Edward
authors.initials: E
authors.lastname: Eivers
authors.forename: Keith E
authors.initials: KE
authors.lastname: Blackwell
authors.forename: David B
authors.initials: DB
authors.lastname: Keschner
authors.forename: Rohit
authors.initials: R
authors.lastname: Garg
authors.forename: Edith
authors.initials: E
authors.lastname: Porter
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D002908:Chronic Disease; D015870:Gene Expression; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D009092:Mucous Membrane / Q000276:immunology / Q000378:metabolism; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology; D010256:Paranasal Sinuses / Q000276:immunology / Q000378:metabolism; D012220:Rhinitis / Q000276:immunology*; D012269:Ribosomal Proteins / Q000378:metabolism; D012852:Sinusitis / Q000276:immunology*; D002785:Sterol O-Acyltransferase / Q000378:metabolism; D015854:Up-Regulation; D023084:alpha-Defensins / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D012269:Ribosomal Proteins; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; C406427:human neutrophil peptide 3; C054675:ribosomal protein P0; D002785:Sterol O-Acyltransferase; C493492:sterol O-acyltransferase 1
keywords: cholesteryl esters; chronic rhinosinusitis; defensin; epithelial antimicrobial factors; mucosa