title: Lymphocyte CFTR promotes epithelial bicarbonate secretion for bacterial killing.
abstract: The expression of cystic fibrosis transmembrane conductance regulator (CFTR) in lymphocytes has been reported for nearly two decades; however, its physiological role remains elusive. Here, we report that co-culture of lymphocytes with lung epithelial cell line, Calu-3, promotes epithelial HCO(3)- production/secretion with up-regulated expression of carbonic anhydrase 2 and 4 (CA-2, CA-4) and enhanced bacterial killing capability. The lymphocyte-enhanced epithelial HCO(3)- secretion and bacterial killing activity was abolished when Calu3 cells were co-cultured with lymphocytes from CFTR knockout mice, or significantly reduced by interfering with E-cadherin, a putative binding partner of CFTR. Bacterial lipopolysaccharide (LPS)-induced E-cadherin and CA-4 expression in the challenged lung was also found to be impaired in CFTR knockout mice compared to that of the wild-type. These results suggest that the interaction between lymphocytes and epithelial cells may induce a previously unsuspected innate host defense mechanism against bacterial infection by stimulating epithelial HCO(3)- production/secretion, which requires CFTR expression in lymphocytes.
authors.affiliation: Epithelial Cell Biology Research Center, School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, NT, HKSAR, Hong Kong, China.
authors.forename: Xiao Xiao
authors.initials: XX
authors.lastname: Tang
authors.forename: Kin Lam
authors.initials: KL
authors.lastname: Fok
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.forename: Kay Sheung
authors.initials: KS
authors.lastname: Chan
authors.forename: Lai Ling
authors.initials: LL
authors.lastname: Tsang
authors.forename: Dewi Kenneth
authors.initials: DK
authors.lastname: Rowlands
authors.forename: Xiao Hu
authors.initials: XH
authors.lastname: Zhang
authors.forename: Jian Da
authors.initials: JD
authors.lastname: Dong
authors.forename: Ye Chun
authors.initials: YC
authors.lastname: Ruan
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Jiang
authors.forename: Sidney Siu Bun
authors.initials: SS
authors.lastname: Yu
authors.forename: Yiu Wa
authors.initials: YW
authors.lastname: Chung
authors.forename: Hsiao Chang
authors.initials: HC
authors.lastname: Chan
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D002256:Carbonic Anhydrases / Q000378:metabolism; D002460:Cell Line; D002692:Chlamydia trachomatis / Q000276:immunology; D018920:Coculture Techniques; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008214:Lymphocytes / Q000166:cytology / Q000502:physiology*; D051379:Mice; D018181:Mice, Inbred CFTR; D018345:Mice, Knockout; D011550:Pseudomonas aeruginosa / Q000276:immunology; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism
chemical_list: D001639:Bicarbonates; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D002256:Carbonic Anhydrases