Bronchial epithelial injury in the context of alloimmunity promotes lymphocytic bronchiolitis through hyaluronan expression

Stober, Vandy P.; Szczesniak, Christopher; Childress, Quiana; Heise, Rebecca L.; Bortner, Carl D.; Hollingsworth, John W.; Neuringer, Isabel P.; Palmer, Scott M.; Garantziotis, Stavros

doi:10.1152/ajplung.00353.2013

Cited by 12 publications

(8 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other possible mechanisms include mitochondrial transfer to rescue stressed cells and improve cellular bioenergetics and function to allow for more efficient repair, as has been elegantly demonstrated previously [44] . Oxidative stress of lung epithelium has been demonstrated in humans with OB after lung transplant and in mice with induced alloimmune activation [45] , [46] , [47] . In addition, we have previously shown that the lungs are under oxidative stress after BMT in our mouse model and that this could be normalized by treatment with KGF, a factor typically secreted by MSCs [48] .…”

Section: Discussionmentioning

confidence: 99%

MSC Therapy Attenuates Obliterative Bronchiolitis after Murine Bone Marrow Transplant

Raza

Trevor²,

Samaratunga³

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

RationaleObliterative bronchiolitis (OB) is a significant cause of morbidity and mortality after lung transplant and hematopoietic cell transplant. Mesenchymal stromal cells (MSCs) have been shown to possess immunomodulatory properties in chronic inflammatory disease.ObjectiveAdministration of MSCs was evaluated for the ability to ameliorate OB in mice using our established allogeneic bone marrow transplant (BMT) model.MethodsMice were lethally conditioned and received allogeneic bone marrow without (BM) or with spleen cells (BMS), as a source of OB-causing T-cells. Cell therapy was started at 2 weeks post-transplant, or delayed to 4 weeks when mice developed airway injury, defined as increased airway resistance measured by pulmonary function test (PFT). BM-derived MSC or control cells [mouse pulmonary vein endothelial cells (PVECs) or lung fibroblasts (LFs)] were administered. Route of administration [intratracheally (IT) and IV] and frequency (every 1, 2 or 3 weeks) were compared. Mice were evaluated at 3 months post-BMT.Measurements and Main ResultsNo ectopic tissue formation was identified in any mice. When compared to BMS mice receiving control cells or no cells, those receiving MSCs showed improved resistance, compliance and inspiratory capacity. Interim PFT analysis showed no difference in route of administration. Improvements in PFTs were found regardless of dose frequency; but once per week worked best even when administration began late. Mice given MSC also had decreased peribronchiolar inflammation, lower levels of hydroxyproline (collagen) and higher frequencies of macrophages staining for the alternatively activated macrophage (AAM) marker CD206.ConclusionsThese results warrant study of MSCs as a potential management option for OB in lung transplant and BMT recipients.

show abstract

Section: Discussionmentioning

confidence: 99%

MSC Therapy Attenuates Obliterative Bronchiolitis after Murine Bone Marrow Transplant

Raza

Trevor²,

Samaratunga³

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Pep-1 efficiently inhibited dendritic cell-dependent cluster formation, IL-2 and IFN-γ production, and T cell proliferation [299]. Moreover, Pep-1 ameliorated naphthalene-induced lymphocytic bronchitis in a mouse model [300]. …”

Section: Ha As Therapeuticmentioning

confidence: 99%

Hyaluronan as a therapeutic target in human diseases

Liang

Jiang

Noble

2016

Advanced Drug Delivery Reviews

178

117

View full text Add to dashboard Cite

Accumulation and turnover of extracellular matrix is a hallmark of tissue injury, repair and remodeling in human diseases. Hyaluronan is a major component of the extracellular matrix and plays an important role in regulating tissue injury and repair, and controlling disease outcomes. The function of hyaluronan depends on its size, location, and interactions with binding partners. While fragmented hyaluronan stimulates the expression of an array of genes by a variety of cell types regulating inflammatory responses and tissue repair, cell surface hyaluronan provides protection against tissue damage from the environment and promotes regeneration and repair. The interactions of hyaluronan and its binding proteins participate in the pathogenesis of many human diseases. Thus, targeting hyaluronan and its interactions with cells and proteins may provide new approaches to developing therapeutics for inflammatory and fibrosing diseases. This review focuses on the role of hyaluronan in biological and pathological processes, and as a potential therapeutic target in human diseases.

show abstract

“…( 36 ). HA cables have been induced in a variety of cell types in vitro , including smooth muscle cells from the lung ( 37 ) and colon ( 32 ), in airway ( 38 ) and renal epithelial cells ( 39 ), as well as epidermal keratinocytes ( 40 ). However, HA cables have yet to be described in vivo , although HA and IαI co-staining has been reported in a human case of inflammatory bowel disease ( 32 ).…”

Section: The Different Forms Of Hamentioning

confidence: 99%

The Where, When, How, and Why of Hyaluronan Binding by Immune Cells

et al. 2015

View full text Add to dashboard Cite

Hyaluronan is made and extruded from cells to form a pericellular or extracellular matrix (ECM) and is present in virtually all tissues in the body. The size and form of hyaluronan present in tissues are indicative of a healthy or inflamed tissue, and the interactions of hyaluronan with immune cells can influence their response. Thus, in order to understand how inflammation is regulated, it is necessary to understand these interactions and their consequences. Although there is a large turnover of hyaluronan in our bodies, the large molecular mass form of hyaluronan predominates in healthy tissues. Upon tissue damage and/or infection, the ECM and hyaluronan are broken down and an inflammatory response ensues. As inflammation is resolved, the ECM is restored, and high molecular mass hyaluronan predominates again. Immune cells encounter hyaluronan in the tissues and lymphoid organs and respond differently to high and low molecular mass forms. Immune cells differ in their ability to bind hyaluronan and this can vary with the cell type and their activation state. For example, peritoneal macrophages do not bind soluble hyaluronan but can be induced to bind after exposure to inflammatory stimuli. Likewise, naïve T cells, which typically express low levels of the hyaluronan receptor, CD44, do not bind hyaluronan until they undergo antigen-stimulated T cell proliferation and upregulate CD44. Despite substantial knowledge of where and when immune cells bind hyaluronan, why immune cells bind hyaluronan remains a major outstanding question. Here, we review what is currently known about the interactions of hyaluronan with immune cells in both healthy and inflamed tissues and discuss how hyaluronan binding by immune cells influences the inflammatory response.

show abstract

Bronchial epithelial injury in the context of alloimmunity promotes lymphocytic bronchiolitis through hyaluronan expression

Cited by 12 publications

References 29 publications

MSC Therapy Attenuates Obliterative Bronchiolitis after Murine Bone Marrow Transplant

MSC Therapy Attenuates Obliterative Bronchiolitis after Murine Bone Marrow Transplant

Hyaluronan as a therapeutic target in human diseases

The Where, When, How, and Why of Hyaluronan Binding by Immune Cells

Contact Info

Product

Resources

About