Limits...
The Rise and Fall of Hyaluronan in Respiratory Diseases.

Lauer ME, Dweik RA, Garantziotis S, Aronica MA - Int J Cell Biol (2015)

Bottom Line: The HA that accumulates in inflamed airways is of a high molecular weight (>1600 kDa) but can be broken down into smaller fragments (<150 kDa) by inflammatory and disease-related mechanisms that have profound effects on HA pathobiology.During inflammation in the airways, HA is often covalently modified with heavy chains from inter-alpha-inhibitor via the enzyme tumor-necrosis-factor-stimulated-gene-6 (TSG-6) and this modification promotes the interaction of leukocytes with HA matrices at sites of inflammation.The clearance of HA and its return to normal levels is essential for the proper resolution of inflammation.

View Article: PubMed Central - PubMed

Affiliation: Pediatric Institute, Cleveland Clinic, Cleveland, OH 44195, USA ; Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH 44195, USA.

ABSTRACT
In normal airways, hyaluronan (HA) matrices are primarily located within the airway submucosa, pulmonary vasculature walls, and, to a lesser extent, the alveoli. Following pulmonary injury, elevated levels of HA matrices accumulate in these regions, and in respiratory secretions, correlating with the extent of injury. Animal models have provided important insight into the role of HA in the onset of pulmonary injury and repair, generally indicating that the induction of HA synthesis is an early event typically preceding fibrosis. The HA that accumulates in inflamed airways is of a high molecular weight (>1600 kDa) but can be broken down into smaller fragments (<150 kDa) by inflammatory and disease-related mechanisms that have profound effects on HA pathobiology. During inflammation in the airways, HA is often covalently modified with heavy chains from inter-alpha-inhibitor via the enzyme tumor-necrosis-factor-stimulated-gene-6 (TSG-6) and this modification promotes the interaction of leukocytes with HA matrices at sites of inflammation. The clearance of HA and its return to normal levels is essential for the proper resolution of inflammation. These data portray HA matrices as an important component of normal airway physiology and illustrate its integral roles during tissue injury and repair among a variety of respiratory diseases.

No MeSH data available.


Related in: MedlinePlus

Mechanistic role of HA in the response to lung injury: lung injury leads to the synthesis of HA that accumulates in the peribronchial and perivascular spaces. The ongoing inflammation leads to the generation of heavy-chain-HA (HC-HA) complexes mediated via TSG-6 which is a bottleneck in the pathological transformation of HA matrices. These HC-HA complexes can be degraded into smaller LMW fragments which engage cell receptors such as CD44, TLR4, and TLR2 and create downstream biological effects like fibrosis, AHR, and inflammation.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4581576&req=5

fig2: Mechanistic role of HA in the response to lung injury: lung injury leads to the synthesis of HA that accumulates in the peribronchial and perivascular spaces. The ongoing inflammation leads to the generation of heavy-chain-HA (HC-HA) complexes mediated via TSG-6 which is a bottleneck in the pathological transformation of HA matrices. These HC-HA complexes can be degraded into smaller LMW fragments which engage cell receptors such as CD44, TLR4, and TLR2 and create downstream biological effects like fibrosis, AHR, and inflammation.

Mentions: These studies indicate that (i) elevated levels of HA in BAL fluid are associated with a variety of environmental and occupational airway injuries. (ii) HA levels correspond to the extent of exposure and lung injury. And (iii) elevated HA levels in BAL may be present even in the absence of obvious lung disease. As shown in Figure 1, one of the host responses of the airways to occupational and environmental exposures is the production of HA in the lung tissue and pulmonary secretions. If the exposure continues, and inflammation fails to resolve, abnormal matrix remodeling occurs, including the chronic synthesis of HA, its modification with the heavy chains of inter-alpha-inhibitor, and the production of proinflammatory HA fragments which exacerbates the inflammatory and fibrotic stimuli [9, 39–45] (Figure 2). It should be noted that the role of heavy chain modified HA fragments in directing inflammatory events has not yet been elucidated.


The Rise and Fall of Hyaluronan in Respiratory Diseases.

Lauer ME, Dweik RA, Garantziotis S, Aronica MA - Int J Cell Biol (2015)

Mechanistic role of HA in the response to lung injury: lung injury leads to the synthesis of HA that accumulates in the peribronchial and perivascular spaces. The ongoing inflammation leads to the generation of heavy-chain-HA (HC-HA) complexes mediated via TSG-6 which is a bottleneck in the pathological transformation of HA matrices. These HC-HA complexes can be degraded into smaller LMW fragments which engage cell receptors such as CD44, TLR4, and TLR2 and create downstream biological effects like fibrosis, AHR, and inflammation.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4581576&req=5

fig2: Mechanistic role of HA in the response to lung injury: lung injury leads to the synthesis of HA that accumulates in the peribronchial and perivascular spaces. The ongoing inflammation leads to the generation of heavy-chain-HA (HC-HA) complexes mediated via TSG-6 which is a bottleneck in the pathological transformation of HA matrices. These HC-HA complexes can be degraded into smaller LMW fragments which engage cell receptors such as CD44, TLR4, and TLR2 and create downstream biological effects like fibrosis, AHR, and inflammation.
Mentions: These studies indicate that (i) elevated levels of HA in BAL fluid are associated with a variety of environmental and occupational airway injuries. (ii) HA levels correspond to the extent of exposure and lung injury. And (iii) elevated HA levels in BAL may be present even in the absence of obvious lung disease. As shown in Figure 1, one of the host responses of the airways to occupational and environmental exposures is the production of HA in the lung tissue and pulmonary secretions. If the exposure continues, and inflammation fails to resolve, abnormal matrix remodeling occurs, including the chronic synthesis of HA, its modification with the heavy chains of inter-alpha-inhibitor, and the production of proinflammatory HA fragments which exacerbates the inflammatory and fibrotic stimuli [9, 39–45] (Figure 2). It should be noted that the role of heavy chain modified HA fragments in directing inflammatory events has not yet been elucidated.

Bottom Line: The HA that accumulates in inflamed airways is of a high molecular weight (>1600 kDa) but can be broken down into smaller fragments (<150 kDa) by inflammatory and disease-related mechanisms that have profound effects on HA pathobiology.During inflammation in the airways, HA is often covalently modified with heavy chains from inter-alpha-inhibitor via the enzyme tumor-necrosis-factor-stimulated-gene-6 (TSG-6) and this modification promotes the interaction of leukocytes with HA matrices at sites of inflammation.The clearance of HA and its return to normal levels is essential for the proper resolution of inflammation.

View Article: PubMed Central - PubMed

Affiliation: Pediatric Institute, Cleveland Clinic, Cleveland, OH 44195, USA ; Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH 44195, USA.

ABSTRACT
In normal airways, hyaluronan (HA) matrices are primarily located within the airway submucosa, pulmonary vasculature walls, and, to a lesser extent, the alveoli. Following pulmonary injury, elevated levels of HA matrices accumulate in these regions, and in respiratory secretions, correlating with the extent of injury. Animal models have provided important insight into the role of HA in the onset of pulmonary injury and repair, generally indicating that the induction of HA synthesis is an early event typically preceding fibrosis. The HA that accumulates in inflamed airways is of a high molecular weight (>1600 kDa) but can be broken down into smaller fragments (<150 kDa) by inflammatory and disease-related mechanisms that have profound effects on HA pathobiology. During inflammation in the airways, HA is often covalently modified with heavy chains from inter-alpha-inhibitor via the enzyme tumor-necrosis-factor-stimulated-gene-6 (TSG-6) and this modification promotes the interaction of leukocytes with HA matrices at sites of inflammation. The clearance of HA and its return to normal levels is essential for the proper resolution of inflammation. These data portray HA matrices as an important component of normal airway physiology and illustrate its integral roles during tissue injury and repair among a variety of respiratory diseases.

No MeSH data available.


Related in: MedlinePlus