title: Hyaluronan Rafts on Airway Epithelial Cells.
abstract: Many cells, including murine airway epithelial cells, respond to a variety of inflammatory stimuli by synthesizing leukocyte-adhesive hyaluronan (HA) cables that remain attached to their cell surfaces. This study shows that air-liquid interface cultures of murine airway epithelial cells (AECs) also actively synthesize and release a majority of their HA onto their ciliated apical surfaces to form a heavy chain hyaluronan (HC-HA) matrix in the absence of inflammatory stimuli. These matrices do not resemble the rope-like HA cables but occur in distinct sheets or rafts that can capture and embed leukocytes from cell suspensions. The HC-HA modification involves the transfer of heavy chains from the inter-α-inhibitor (IαI) proteoglycan, which has two heavy chains (HC1 and HC2) on its chondroitin sulfate chain. The transesterification transfer of HCs from chondroitin sulfate to HA is mediated by tumor necrosis factor-induced gene 6 (TSG-6), which is up-regulated in inflammatory reactions. Because the AEC cultures do not have TSG-6 nor serum, the source of IαI, assays for HCs and TSG-6 were done. The results show that AECs synthesize TSG-6 and their own heavy chain donor (pre-IαI) with a single heavy chain 3 (HC3), which are also constitutively expressed by human renal proximal tubular epithelial cells. These leukocyte adhesive HC3-HA structures were also found in the bronchoalveolar lavage of naïve mice and were observed on their apical ciliated surfaces. Thus, these leukocyte-adhesive HA rafts are now identified as HC3-HA complexes that could be part of a host defense mechanism filling some important gaps in our current understanding of murine airway epithelial biology and secretions.
authors.affiliation: From the Department of Biomedical Engineering and Department of Chemistry, Cleveland State University, Cleveland, Ohio 44115.
authors.forename: Amina
authors.initials: A
authors.lastname: Abbadi
authors.affiliation: From the Department of Biomedical Engineering and.
authors.forename: Mark
authors.initials: M
authors.lastname: Lauer
authors.affiliation: Department of Pathobiology, Cleveland Clinic, Cleveland, Ohio 44195 and.
authors.forename: Shadi
authors.initials: S
authors.lastname: Swaidani
authors.affiliation: From the Department of Biomedical Engineering and.
authors.forename: Aimin
authors.initials: A
authors.lastname: Wang
authors.affiliation: From the Department of Biomedical Engineering and hascalv@ccf.org.
authors.forename: Vincent
authors.initials: V
authors.lastname: Hascall
mesh_terms: D000510:Alpha-Globulins / Q000378:metabolism; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000276:immunology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D016764:Cell Polarity; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000378:metabolism*; D018928:Immunity, Mucosal; D008297:Male; D021962:Membrane Microdomains / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008970:Molecular Weight; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D014132:Trachea / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
chemical_list: D000510:Alpha-Globulins; D015815:Cell Adhesion Molecules; D011509:Proteoglycans; C513057:Tnfaip6 protein, mouse; C016001:alpha-1-microglobulin; C011877:inter-alpha-inhibitor; D006820:Hyaluronic Acid
keywords: TSG-6; airway epithelium; cell surface; epithelial cell; heavy chains; host defense; hyaluronan; hyaluronan raft; lung; pre-α-inhibitor