Hyaluronan Rafts on Airway Epithelial Cells

Abbadi, Amina; Lauer, Mark E.; Swaidani, Shadi; Wang, Aimin; Hascall, Vincent C.

doi:10.1074/jbc.m115.704288

Cited by 17 publications

(15 citation statements)

References 40 publications

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“…34, 35 Recently, Abbadi et al reported that lung epithelial cells also synthesize cell surface glycocalyx of HC3-HA (HA-Raft) that traps leukocytes; thus, it might have a role in host defense. 36 Our observation of the presence of the HC-HA/PTX3 complex on UMSCs is consistent with the idea that such complexes may account for the ability of UMSCs to modulate host inflammation and immune responses.…”

Section: Use Of Umsc and Bmsc For Treating Congenital Corneal Diseases‡supporting

confidence: 89%

Cell Therapy of Corneal Diseases

Kao

Coulson‐Thomas²

2016

Cornea

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Mesenchymal stem cells (MSC) isolated from connective tissues are pluripotent and differentiate to phenotypes of connective tissue cell lineages (osteoblasts, chondrocytes, adipocytes) in vitro and in vivo. They have been used to treat mouse models of connective tissue disease such as Lumican null (Lum−/−), and mucopolysaccharidosis (Gusb) mice. MSC have unique immunosuppressive properties allowing evasion of host rejection; thus, they are valuable tools for cell therapy of congenital and acquired diseases involving immune dysfunction of multiple tissues including ocular surface tissues (cornea). We previously showed that human umbilical mesenchymal stem cells (UMSCs) modulated host immune responses, enabling them to survive xenograft transplantations. In vitro UMSCs modulated inflammatory cells by inhibiting adhesion and invasion, and inducing cell death. UMSC also regulated M1/M2 macrophage polarization and induced T-regulatory cell maturation from naïve intraperitoneal cavity lavage cells. UMSCs exposed to inflammatory cells synthesized a rich extracellular glycocalyx composed of hyaluronan (HA) bound to the heavy chains (HCs) of inter-alpha-trypsin inhibitor (HC-HA), which contains tumor necrosis factorα-stimulated gene 6 (TSG6) that catalyzes the transfer of HCs to HA, versican and pentraxin-3. Our in vivo and in vitro results showed that glycocalyx regulated inflammatory cells, allowing UMSCs to survive host immune rejection. Administration of antibodies against glycocalyx constituents or digestion with hyaluronidase and chondroitinase ABC abolished the UMSC ability to modulate immune responses. Treatment with anti-CD44 antibodies also diminished modulation of M2 macrophages by UMSC, indicating cell surface CD44 is required for correct UMSC glycocalyx assembly to modulate inflammatory cells.

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Section: Use Of Umsc and Bmsc For Treating Congenital Corneal Diseases‡supporting

confidence: 89%

Cell Therapy of Corneal Diseases

Kao

Coulson‐Thomas²

2016

Cornea

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“…Constitutive HC•HA formation is associated with murine airway epithelial cells (AECs) and human renal proximal tubular ECs, both of which make HC3•HA, through constitutively expressing PI and TSG-6 [110]. AECs in culture assemble the HC3•HA complexes into raft-like structures on their ciliated apical surface that can capture and entrap leukocytes.…”

Section: The Role Of Tsg-6 In Hc•ha Formation 421 the Structural And Functional Diversity Of Hc•hasmentioning

confidence: 99%

TSG-6: A multifunctional protein with anti-inflammatory and tissue-protective properties

2019

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Tumor necrosis factor- (TNF) stimulated gene-6 (TSG-6) is an inflammation-associated secreted protein that has been implicated as having important and diverse tissue protective and anti-inflammatory properties, e.g. mediating many of the immunomodulatory and beneficial activities of mesenchymal stem/stromal cells. TSG-6 is constitutively expressed in some tissues, which are either highly metabolically active or subject to challenges from the environment, perhaps providing protection in these contexts. The diversity of its functions are dependent on the binding of TSG-6 to numerous ligands, including matrix molecules such as glycosaminoglycans, as well as immune regulators and growth factors that themselves interact with these linear polysaccharides. It is becoming apparent that TSG-6 can directly affect matrix structure and modulate the way extracellular signalling molecules interact with matrix. In this review, we focus mainly on the literature for TSG-6 over the last 10 years, summarizing its expression, structure, ligand-binding properties, biological functions and highlighting TSG-6's potential as a therapeutic for a broad range of disease indications.

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“…Type II alveolar epithelial cells (AECs) express HAS2 and surface HA ( 17 ). HA is loosely attached and shed from the apical surface of primary AEC cultures, and can be observed above the airway epithelium ( 18 ), although this is not always the case ( 10 , 12 ). This suggests that HA can be released into the alveolar fluid above the AECs.…”

Section: Hyaluronan In the Healthy Lungmentioning

confidence: 99%

Hyaluronan and Its Interactions With Immune Cells in the Healthy and Inflamed Lung

et al. 2018

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Hyaluronan is a hygroscopic glycosaminoglycan that contributes to both extracellular and pericellular matrices. While the production of hyaluronan is essential for mammalian development, less is known about its interaction and function with immune cells. Here we review what is known about hyaluronan in the lung and how it impacts immune cells, both at homeostasis and during lung inflammation and fibrosis. In the healthy lung, alveolar macrophages provide the first line of defense and play important roles in immunosurveillance and lipid surfactant homeostasis. Alveolar macrophages are surrounded by a coat of hyaluronan that is bound by CD44, a major hyaluronan receptor on immune cells, and this interaction contributes to their survival and the maintenance of normal alveolar macrophage numbers. Alveolar macrophages are conditioned by the alveolar environment to be immunosuppressive, and can phagocytose particulates without alerting an immune response. However, during acute lung infection or injury, an inflammatory immune response is triggered. Hyaluronan levels in the lung are rapidly increased and peak with maximum leukocyte infiltration, suggesting a role for hyaluronan in facilitating leukocyte access to the injury site. Hyaluronan can also be bound by hyaladherins (hyaluronan binding proteins), which create a provisional matrix to facilitate tissue repair. During the subsequent remodeling process hyaluronan concentrations decline and levels return to baseline as homeostasis is restored. In chronic lung diseases, the inflammatory and/or repair phases persist, leading to sustained high levels of hyaluronan, accumulation of associated immune cells and an inability to resolve the inflammatory response.

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Hyaluronan Rafts on Airway Epithelial Cells

Cited by 17 publications

References 40 publications

Cell Therapy of Corneal Diseases

Cell Therapy of Corneal Diseases

TSG-6: A multifunctional protein with anti-inflammatory and tissue-protective properties

Hyaluronan and Its Interactions With Immune Cells in the Healthy and Inflamed Lung

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