Specific binding of IL-8 to rabbit α -macroglobulin modulates IL-8 function in the lung

Kurdowska, Anna; Fujisawa, Nobumitsu; Peterson, Barry T.; Carr, Ferdicia K.; Noble, James M.; Alden, Susanne M; Miller, Edmund J.; Teodorescu, M.

doi:10.1007/s000110050636

Cited by 10 publications

(5 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, this is the first study to define the activity of IL-8 in ␣ 2 -M/IL-8 complexes purified from pulmonary edema fluid. Thus our observations are more closely related to in vivo conditions than our prior studies of the in vitro activity of IL-8 (13)(14)(15).…”

Section: Discussionsupporting

confidence: 62%

See 1 more Smart Citation

Activity of pulmonary edema fluid interleukin-8 bound to α₂-macroglobulin in patients with acute lung injury

Kurdowska

Geiser

Alden

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

The formation of alpha(2)-macroglobulin (alpha(2)-M)/interleukin-8 (IL-8) complexes may influence the biological activity of IL-8 and the quantitative assessment of IL-8 activity. Therefore, in this study, concentrations of free IL-8 and IL-8 complexes with alpha(2)-M were measured in pulmonary edema fluid samples from patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) and compared with control patients with hydrostatic pulmonary edema. Patients with ALI/ARDS had significantly higher concentrations of alpha(2)-M (P < 0.01) as well as alpha(2)-M/IL-8 complexes (P < 0.05). Because a substantial amount of IL-8 is complexed to alpha(2)-M, standard assays of free IL-8 may significantly underestimate the concentration of biologically active IL-8 in the distal air spaces of patients with ALI/ARDS. Furthermore, IL-8 bound to alpha(2)-M retained its biological activity, and this fraction of IL-8 was protected from proteolytic degradation. Thus complex formation may modulate the acute inflammatory process in the lung.

show abstract

Section: Discussionsupporting

confidence: 62%

“…On the other hand, our previous findings suggested that ␣ 2 -M could be an important mediator of IL-8 clearance (13,15). Those studies indicated that alveolar macrophages have receptors for ␣ 2 -M but not for IL-8.…”

Section: Discussionmentioning

confidence: 92%

Activity of pulmonary edema fluid interleukin-8 bound to α₂-macroglobulin in patients with acute lung injury

Kurdowska

Geiser

Alden

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…CXCR1 is specific for IL-8 (40,41), and within this study we have found that IL-8 interacts with glycosylated AAT, but rather than facilitating IL-8 activity, physiological concentrations of AAT inhibit CXCR1 engagement of up to 20 ng of IL-8, thereby preventing downstream signaling events including Akt phosphorylation, calcium flux, and chemoattractant-induced cytoskeletal rearrangements. This antiinflammatory effect is not exclusive to AAT, as it has also been reported that the plasma glycoprotease inhibitor α-2 macroglobulin creates a complex with IL-8, resulting in reduced neutrophil infiltration into the lungs compared with IL-8 controls (42). AAT and α-2 macroglobulin are acute-phase reactants, and as both proteins show a rise in mean value after infection, it is tempting to speculate that the increased levels of both serum proteins function to dampen down the inflammatory response after infection by binding and inactivating IL-8 activity.…”

Section: Discussionmentioning

confidence: 70%

α-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8

Bergin¹,

Reeves²,

Meleady³

et al. 2010

J. Clin. Invest.

254

305

View full text Add to dashboard Cite

Hereditary deficiency of the protein α-1 antitrypsin (AAT) causes a chronic lung disease in humans that is characterized by excessive mobilization of neutrophils into the lung. However, the reason for the increased neutrophil burden has not been fully elucidated. In this study we have demonstrated using human neutrophils that serum AAT coordinates both CXCR1-and soluble immune complex (sIC) receptor-mediated chemotaxis by divergent pathways. We demonstrated that glycosylated AAT can bind to IL-8 (a ligand for CXCR1) and that AAT-IL-8 complex formation prevented IL-8 interaction with CXCR1. Second, AAT modulated neutrophil chemotaxis in response to sIC by controlling membrane expression of the glycosylphosphatidylinositolanchored (GPI-anchored) Fc receptor FcγRIIIb. This process was mediated through inhibition of ADAM-17 enzymatic activity. Neutrophils isolated from clinically stable AAT-deficient patients were characterized by low membrane expression of FcγRIIIb and increased chemotaxis in response to IL-8 and sIC. Treatment of AATdeficient individuals with AAT augmentation therapy resulted in increased AAT binding to IL-8, increased AAT binding to the neutrophil membrane, decreased FcγRIIIb release from the neutrophil membrane, and normalization of chemotaxis. These results provide new insight into the mechanism underlying the effect of AAT augmentation therapy in the pulmonary disease associated with AAT deficiency.

show abstract

“…There are many reports describing the effects of clusterin, haptoglobin and α 2 M on the immune system (59,(176)(177)(178)(179)(180). Some of these, such as the ability of α 2 M to enhance antigen presentation (91) and haptoglobin-facilitated clearance of hemoglobin (180), clearly fall outside of the scope of this review and as such, will not be discussed here.…”

Section: Anti-inflammatory Effects Of Ecsmentioning

confidence: 99%

Extracellular Chaperones and Proteostasis

Wyatt

Yerbury

Ecroyd

et al. 2013

Annu. Rev. Biochem.

161

173

View full text Add to dashboard Cite

There is a family of currently untreatable serious human diseases that arise from the inappropriate misfolding and aggregation of extracellular proteins. At present our understanding of mechanisms that operate to maintain proteostasis in extracellular body fluids is limited but has significantly advanced with the discovery of a small but growing family of constitutively secreted extracellular chaperones (ECs). The available evidence strongly suggests that these chaperones act as both sensors and disposal-mediators of misfolded proteins in extracellular fluids, thereby normally protecting us from disease pathologies. It is critically important to further increase our understanding of the mechanisms that operate to effect extracellular proteostasis, as this will be essential knowledge upon which to base the development of effective therapies for some of the world's most debilitating, costly and intractable diseases.

show abstract

Specific binding of IL-8 to rabbit α -macroglobulin modulates IL-8 function in the lung

Abstract: The data suggest that alphaM may facilitate IL-8 clearance from the lung.

Cited by 10 publications

References 43 publications

Activity of pulmonary edema fluid interleukin-8 bound to α₂-macroglobulin in patients with acute lung injury

Activity of pulmonary edema fluid interleukin-8 bound to α₂-macroglobulin in patients with acute lung injury

α-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8

Extracellular Chaperones and Proteostasis

Contact Info

Product

Resources

About

Specific binding of IL-8 to rabbit α -macroglobulin modulates IL-8 function in the lung

Abstract: The data suggest that alphaM may facilitate IL-8 clearance from the lung.

Cited by 10 publications

References 43 publications

Activity of pulmonary edema fluid interleukin-8 bound to α2-macroglobulin in patients with acute lung injury

Activity of pulmonary edema fluid interleukin-8 bound to α2-macroglobulin in patients with acute lung injury

α-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8

Extracellular Chaperones and Proteostasis

Contact Info

Product

Resources

About

Activity of pulmonary edema fluid interleukin-8 bound to α₂-macroglobulin in patients with acute lung injury

Activity of pulmonary edema fluid interleukin-8 bound to α₂-macroglobulin in patients with acute lung injury