A Role for Hyaluronan in Macrophage Accumulation and Collagen Deposition after Bleomycin-Induced Lung Injury

Savani, Rashmin C.; Hou, Guangpei; Liu, Ping; Wang, Chao; Simons, Elinor; Grimm, Paul; Stern, Robert; Greenberg, Arnold H.; DeLisser, Horace M.; Khalil, Nasreen

doi:10.1165/ajrcmb.23.4.3944

Cited by 74 publications

(79 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This reagent has been used previously to bind HA and attenuate the biological effects of this molecule (16). Immunohistochemical staining demonstrated that HABP significantly attenuated CD44-hyaluronan binding on alveolar macrophages after ozone exposure, compared with scrambled control peptide or saline (Fig.…”

Section: Ha Recognition Is Required For the Development Of Ahr Aftermentioning

confidence: 94%

Hyaluronan Mediates Ozone-induced Airway Hyperresponsiveness in Mice

Garantziotis

Potts

et al. 2009

Journal of Biological Chemistry

Self Cite

113

136

View full text Add to dashboard Cite

Ozone is a common urban environmental air pollutant and significantly contributes to hospitalizations for respiratory illness. The mechanisms, which regulate ozone-induced bronchoconstriction, remain poorly understood. Hyaluronan was recently shown to play a central role in the response to noninfectious lung injury. Therefore, we hypothesized that hyaluronan contributes to airway hyperreactivity (AHR) after exposure to ambient ozone. Using an established model of ozone-induced airways disease, we characterized the role of hyaluronan in airway hyperresponsiveness. The role of hyaluronan in response to ozone was determined by using therapeutic blockade, genetically modified animals, and direct challenge to hyaluronan. Ozone-exposed mice demonstrate enhanced AHR associated with elevated hyaluronan levels in the lavage fluid. Mice deficient in either CD44 (the major receptor for hyaluronan) or inter-␣-trypsin inhibitor (molecule that facilitates hyaluronan binding) show similar elevations in hyaluronan but are protected from ozone-induced AHR. Mice pretreated with hyaluronan-binding peptide are protected from the development of ozone-induced AHR. Overexpression of hyaluronan enhances the airway response to ozone. Intratracheal instillation of endotoxin-free low molecular weight hyaluronan induces AHR dependent on CD44, whereas instillation of high molecular weight hyaluronan protects against ozone-induced AHR. In conclusion, we demonstrate that hyaluronan mediates ozoneinduced AHR, which is dependent on the fragment size and both CD44 and inter-␣-trypsin inhibitor. These data support the conclusion that pulmonary matrix can contribute to the development of airway hyperresponsiveness.Ozone is a commonly encountered urban air pollutant that significantly contributes to increased morbidity (1-4) and can lead to a significant economic burden. It has been estimated that each year inhalation of ambient ozone contributes to 800 premature deaths, 4,500 hospital admissions, 900,000 school absences, and more than 1 million restricted activity days with an estimated $5 billion annual economic burden (5). Population-based studies suggest that for each 10 ppb increase in 1-h daily maximum level of ozone there is an increase in mortality risk of 0.39 -0.87%, especially in individuals with pre-existing respiratory disease (2, 3, 6, 7). However, the biological mechanisms, which regulate the response to ambient ozone exposure, remain poorly understood.Hyaluronan is an abundant extracellular matrix component, which has been recently shown to play a significant role in the response to noninfectious lung injury. Short fragment hyaluronan (sHA) 2 is released in the lung after sterile injury such as bleomycin instillation (8) or high tidal volume ventilation (9) and can modify the tissue response to injury. Furthermore, hyaluronan has been identified in airway secretions from asthmatics (10), and high molecular weight hyaluronan can attenuate the bronchoconstrictive response in exercise-induced asthma (11). We therefore hypothesized that...

show abstract

Section: Ha Recognition Is Required For the Development Of Ahr Aftermentioning

confidence: 94%

Hyaluronan Mediates Ozone-induced Airway Hyperresponsiveness in Mice

Garantziotis

Potts

et al. 2009

Journal of Biological Chemistry

Self Cite

113

136

View full text Add to dashboard Cite

show abstract

“…[28][29][30][31] CD44 has been shown to have an important role in the clearance of HA from the airways during bleomycin-or LPS-induced lung inflammation, 8,12 and the accumulation of HA fragments contributes to the perpetuation of inflammation in these models. 12,32 Therefore, we considered it of interest to investigate whether CD44 has a part in the clearance of HA during the resolution phase of S. pneumoniae-induced pneumonia. Indeed, HA levels measured in BALF obtained at 4 or 10 days after sublethal infection were much higher in CD44 KO mice than in WT mice ( Figure 5).…”

Section: Cd44 Deficiency Is Associated With Accumulation Of Ha Fragmementioning

confidence: 99%

The role of CD44 in the acute and resolution phase of the host response during pneumococcal pneumonia

Windt

Hoogendijk

Vos

et al. 2011

Laboratory Investigation

View full text Add to dashboard Cite

Streptococcus pneumoniae is the most prevalent pathogen causing community-acquired pneumonia. CD44 is a transmembrane adhesion molecule, expressed by a wide variety of cell types, that has several functions in innate and adaptive immune responses. In this study, we tested the hypothesis that CD44 is involved in the host response during pneumococcal pneumonia. On intranasal infection with a lethal dose of S. pneumoniae CD44-knockout (KO) mice showed a prolonged survival when compared with wild-type mice, which was accompanied by a diminished pulmonary bacterial growth and reduced dissemination to distant body sites. Whereas, proinflammatory cytokine responses and lung pathology were not affected, CD44 deficiency resulted in increased early neutrophil influx into the lung. In separate experiments, we confirmed a detrimental role of CD44 in host defense against pneumococci during sublethal pneumonia, as demonstrated by an improved capacity of CD44 KO mice to clear a low infectious dose. In addition, CD44 appeared important for the resolution of lung inflammation during sublethal pneumonia, as shown by histopathology of lung tissue slides. In conclusion, we show here that CD44 facilitates bacterial outgrowth and dissemination during pneumococcal pneumonia, which in lethal infection results in a prolonged survival of CD44 KO mice. Moreover, during sublethal pneumonia CD44 contributes to the resolution of the inflammatory response.

show abstract

“…Peptides-HA-binding peptide (HABPep), mimicking a charged sequence previously shown to bind HA (RGG-GRGRRR) (25) and scrambled peptide containing the same amino acids but in a random, non-HA binding order (RGRRGRGRG), have been described previously (14). Peptides were commercially produced to Ͼ95% purity (Invitrogen).…”

Section: Methodsmentioning

confidence: 99%

“…12). An increased recovery of HA in bronchoalveolar lavage has been found in a variety of human lung disorders, such as acute respiratory distress syndrome and occupational lung disorders, and in animal models, such as bleomycin-induced lung injury (13,14). In this rodent model, elevated low molecular weight HA content in bronchoalveolar lavage temporally correlates with an influx of macrophages into the lung.…”

mentioning

confidence: 89%

See 1 more Smart Citation

Toll-like Receptor 2 (TLR2), Transforming Growth Factor-β, Hyaluronan (HA), and Receptor for HA-mediated Motility (RHAMM) Are Required for Surfactant Protein A-stimulated Macrophage Chemotaxis

Foley

Lam

Jiang

et al. 2012

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Background: Surfactant protein A stimulates macrophage chemotaxis. Results: SPA interaction with TLR2 stimulates JNK-and ERK-dependent TGF␤ production, which in turn stimulates RHAMM-and hyaluronan-dependent macrophage chemotaxis. Conclusion: SPA activates a novel and specific pathway to stimulate macrophage chemotaxis. Significance: Uncovering the mechanisms that regulate innate immunity in the lung is crucial for understanding the responses to infection and injury.

show abstract

A Role for Hyaluronan in Macrophage Accumulation and Collagen Deposition after Bleomycin-Induced Lung Injury

Cited by 74 publications

References 68 publications

Hyaluronan Mediates Ozone-induced Airway Hyperresponsiveness in Mice

Hyaluronan Mediates Ozone-induced Airway Hyperresponsiveness in Mice

The role of CD44 in the acute and resolution phase of the host response during pneumococcal pneumonia

Toll-like Receptor 2 (TLR2), Transforming Growth Factor-β, Hyaluronan (HA), and Receptor for HA-mediated Motility (RHAMM) Are Required for Surfactant Protein A-stimulated Macrophage Chemotaxis

Contact Info

Product

Resources

About