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Hyaluronan rafts in airway epithelial cells (1007.6)
Author(s) -
Abbadi Amina,
Lauer Mark,
Swaidani Shadi,
Hascall Vincent
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1007.6
Subject(s) - inflammation , chemistry , extracellular matrix , microbiology and biotechnology , bronchoalveolar lavage , cell , glycosaminoglycan , lung , adhesion , hyaluronic acid , immunology , medicine , biology , anatomy , biochemistry , organic chemistry
Hyaluronan (HA) is a linear, non‐sulfated glycosaminoglycan that is normally formed as a unmodified structure but uniquely modified during inflammation. This modification involves the transfer of heavy chains (HC) from IαI to form HC‐HA complexes mediated by TSG‐6. These complexes are identified in bronchial secretions from asthmatics that also show an up‐regulation in their pulmonary TSG‐6 expression. HC‐HA matrices are leukocyte adhesive as demonstrated in many other pathological conditions including idiopathic arterial pulmonary hypertension, asthma and cystic fibrosis. In all cell types studied to date, the leukocyte‐adhesive HA cables synthesized by these cells remain attached to the cell surface. However, while airway epithelial cells (AECs) also form HA cables on their cell surface in response to a variety of inflammatory stimuli, we have identified that they can also actively release a majority of their leukocyte‐adhesive HA structures into the extracellular space from their apical surface even when cells are not treated with inflammatory stimuli. These matrices do not resemble the rope‐like HA cables, but occur in distinct clumps or rafts of HA that can capture and embed leukocytes from cell suspensions. Not only were these leukocyte adhesive structures observed in vitro but also in the bronchoalveolar lavage of naïve mice. Furthermore, we have been able to identify the synthesis of heavy chain 3, previously reported to be constitutively expressed by human proximal tubular epithelial cells as urinary trypsin inhibitor (UTI), which may directly contribute to heavy chain modification of the HA matrix in lung inflammation. This provides evidence that AECs can manufacture their own HC‐donor. By characterizing the structure of these cell‐free HA rafts, the mechanism by which they are synthesized and their effect on leukocyte activation and behavior, we will have a better understanding of their role in human health and disease.