Glycosaminoglycans, Airways Inflammation and Bronchial Hyperresponsiveness

Lever, Rebecca; Page, Clive

doi:10.1006/pupt.2001.0296

Cited by 41 publications

(34 citation statements)

References 68 publications

(21 reference statements)

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“…This association of equivalent bacterial burdens with major differences in neutrophilic inflammation raises the intriguing possibility that mast cells are antiinflammatory in the context of this chronic infection. Notwithstanding their well-known production of inflammatory mediators, mast cells also secrete antiinflammatory products, including heparin (35), which blunts several manifestations of inflammation when used as a drug (36). Deficiency of histamine in mice lacking histidine decarboxylase in a model of immune complex-induced inflammation also is associated with increased neutrophil infiltration (37).…”

Section: Discussionmentioning

confidence: 99%

Mast Cells Protect Mice from Mycoplasma Pneumonia

Zhang

Lyubynska

et al. 2006

Am J Respir Crit Care Med

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Section: Discussionmentioning

confidence: 99%

Mast Cells Protect Mice from Mycoplasma Pneumonia

Zhang

Lyubynska

et al. 2006

Am J Respir Crit Care Med

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“…30 Beneficial clinical effects of heparin have been demonstrated in certain inflammatory diseases such as asthma. 31 In experimental models, the immunosuppressive properties of heparin can prolong skin allograft survival in mice 32 and cardiac allograft and xenograft survival in rats 33,34 ; however, these studies did not assess arterial pathology. We found that heparin inhibits both the recruitment and accumulation of memory T cells to allogeneic human coronary arteries using a chimeric animal model with IFN-␥-dependent vascular remodeling 15 and CXCR3 chemokine expression within the grafts.…”

Section: Discussionmentioning

confidence: 99%

Heparin Displaces Interferon-γ–Inducible Chemokines (IP-10, I-TAC, and Mig) Sequestered in the Vasculature and Inhibits the Transendothelial Migration and Arterial Recruitment of T Cells

et al. 2006

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Background-Heparin, used clinically as an anticoagulant, also has antiinflammatory properties and has been described to inhibit interferon (IFN)-␥ responses in endothelial cells. We investigated the effects of heparin on the IFN-␥-inducible chemokines IP-10/CXCL10, I-TAC/CXCL11, and Mig/CXCL9, which play important roles in the vascular recruitment of IFN-␥-producing Th1 cells through interactions with their cognate receptor, CXCR3. Methods and Results-Patients undergoing coronary artery bypass grafting were studied because coronary atherosclerosis is recognized as a Th1-type inflammatory disease and the subjects required systemic heparinization. Plasma levels of IP-10, I-TAC, and Mig increased immediately after heparin administration and diminished promptly after heparin antagonism with protamine. These effects were independent of detectable circulating IFN-␥ or the IFN-␥ inducer interleukin-12. We confirmed previous reports that heparin inhibits the IFN-␥-dependent production of CXCR3 chemokine ligands using atherosclerotic coronary arteries in organ culture. In addition to prolonged treatment decreasing chemokine secretion, heparin rapidly displaced membrane-associated IP-10 from cultured endothelial cells that did not express CXCR3 and reduced the IP-10 -dependent transendothelial migration of T helper cells under conditions of venular shear stress. Finally, heparin administration to immunodeficient mouse hosts decreased both the recruitment and accumulation of memory T cells within allogeneic human coronary arteries. Conclusions-Besides

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“…Numerous studies have reported the beneficial effects of heparin in major inflammatory diseases, such as inflammatory bowel disease (50) and asthma (46,51). In human asthma and animal models of experimental asthma (i.e., allergic lung inflammation), heparin inhibits allergen-induced early and late asthmatic responses (8) and exercise-induced bronchoconstriction (6,7,9).…”

Section: Discussionmentioning

confidence: 99%

Endogenous Attenuation of Allergic Lung Inflammation by Syndecan-1

Park

Kheradmand

et al. 2005

The Journal of Immunology

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The airway plays a vital role in allergic lung diseases by responding to inhaled allergens and initiating allergic inflammation. Various proinflammatory functions of the airway epithelium have been identified, but, equally important, anti-inflammatory mechanisms must also exist. We show in this study that syndecan-1, the major heparan sulfate proteoglycan of epithelial cells, attenuates allergic lung inflammation. Our results show that syndecan-1-null mice instilled with allergens exhibit exaggerated airway hyperresponsiveness, glycoprotein hypersecretion, eosinophilia, and lung IL-4 responses. However, administration of purified syndecan-1 ectodomains, but not ectodomain core proteins devoid of heparan sulfate, significantly inhibits these inflammatory responses. Furthermore, syndecan-1 ectodomains are shed into the airway when wild-type mice are intranasally instilled with several biochemically distinct inducers of allergic lung inflammation. Our results also show that syndecan-1 ectodomains bind to the CC chemokines (CCL7, CCL11, and CCL17) implicated in allergic diseases, inhibit CC chemokine-mediated T cell migration, and suppress allergen-induced accumulation of Th2 cells in the lung through their heparan sulfate chains. Together, these findings uncover an endogenous anti-inflammatory mechanism of the airway epithelium where syndecan-1 ectodomains attenuate allergic lung inflammation via suppression of CC chemokine-mediated Th2 cell recruitment to the lung.

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Glycosaminoglycans, Airways Inflammation and Bronchial Hyperresponsiveness

Cited by 41 publications

References 68 publications

Mast Cells Protect Mice from Mycoplasma Pneumonia

Mast Cells Protect Mice from Mycoplasma Pneumonia

Heparin Displaces Interferon-γ–Inducible Chemokines (IP-10, I-TAC, and Mig) Sequestered in the Vasculature and Inhibits the Transendothelial Migration and Arterial Recruitment of T Cells

Endogenous Attenuation of Allergic Lung Inflammation by Syndecan-1

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