Date of Award
Epithelial cells, Hyaluronic acid, Leucocytes, Hyaluronan rafts, airway epithelium, heavy chains, TSG-6, pre-a-inhibitor, Heavy chain3-bikunin
Many cells, including murine airway epithelial cells, respond to a variety of inflammatory stimuli by synthesizing leukocyte-adhesive hyaluronan 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-a-inhibitor (IaI) proteoglycan, which has 2 heavy chains (HC1 and HC2) on its chondroitin sulfate (CS) chain. The tranesterification transfer of HCs from CS to HA is mediated by tumor-necrosis-factor-induced-gene 6 (TSG-6), which is upregulated in inflammatory reactions. Because the AEC cultures do not have TSG-6 nor serum, which is the source of IaI, assays for HCs and TSG-6 were done and showed that AECs synthesize TSG-6 and their own heavy chain donor (pre-IaI) with a single heavy chain 3 (HC3), which is the substrate for transfer to HA to form the H3-HA rafts. This HC3 pre-IaI is also constitutively expressed by human renal proximal tubular epithelial cells. These leukocyte adhesive HC3-HA structures were also found in the bronchoalveolar lavage (BAL) of naive 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
Abbadi, Amineh M., "Hyaluronan Rafts on Airway Epithelial Cells" (2014). ETD Archive. 11.