The Duffy antigen receptor for chemokines in acute renal failure: A facilitator of renal chemokine presentation

Zarbock, Alexander; Schmolke, Mirco; Bockhorn, Susanne Grosse; Scharte, Marion; Buschmann, Kirsten; Ley, Klaus; Singbartl, Kai

doi:10.1097/01.ccm.0000280570.82885.32

Cited by 41 publications

(57 citation statements)

References 37 publications

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“…18 Rather, both murine and preclinical data suggest that erythrocyte DARC modulates chemokine homeostasis by acting as a "chemokine reservoir," [19][20][21][22] binding proinfl ammatory chemokines such as IL-8 when concentration levels are high during tissue infl ammation and then releasing them systemically when levels are low. [23][24][25] In support of this proposed role, murine 40 Nonpulmonary organ failure-free (OFF) days were calculated by subtracting the number of days patients met any Brussels organ failure criteria 41 from the lesser of 28 days or number of days to death. 3 A lower number of VFDs and OFF days represents a worse outcome, and organs and systems were considered failure-free after patients were discharged from the hospital.…”

Section: Discussionmentioning

confidence: 99%

The Association Between a Darc Gene Polymorphism and Clinical Outcomes in African American Patients With Acute Lung Injury

Kangelaris

Sapru

Calfee

et al. 2012

Chest

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A cute lung injury (ALI) is a common and frequently fatal cause of acute respiratory failure, affecting up to 20% of patients who are mechanically ventilated and carrying mortality rates from 30% to 40%. [1][2][3] The burden of ALI morbidity and mortality affects African Americans disproportionately: Compared with Americans of European descent, African Americans suffer at least 50% increased risk of death. 4,5 Although it is not known to what extent genetic susceptibility contributes to differences in ALI mortality, African descent has been associated with a "highexpression profi le" of proinfl ammatory chemokines

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Section: Discussionmentioning

confidence: 99%

The Association Between a Darc Gene Polymorphism and Clinical Outcomes in African American Patients With Acute Lung Injury

Kangelaris

Sapru

Calfee

et al. 2012

Chest

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“…In inflamed kidneys, expression of DARC is induced in interstitial endothelial cells. Consistently, DARC deficiency ameliorated disease in two neutrophil-dependent models of acute renal injury [20]. However, in renal disease models with a predominant infiltration of renal macrophages and T cells, DARC deficiency did not improve renal inflammation.…”

Section: What Are the Roles Of Atypical Nonsignaling Chemokine Recepmentioning

confidence: 69%

Questions about Chemokine and Chemokine Receptor Antagonism in Renal Inflammation

Anders¹,

Sayyed²,

Vielhauer³

2009

Nephron Exp Nephrol

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Chemokines remain attractive therapeutic targets for modulating inflammatory diseases in all areas of medicine including acute and chronic kidney disease. Industry has launched huge programs for the development of chemokine antagonists, and clinical trials with chemokine and chemokine receptor antagonists are ongoing. However, chemokine biology remains an area of unexpected discoveries. Here we discuss a number of questions which need to be addressed to further explore the potential of chemokine antagonism in renal inflammation: Why does renal expression of chemokines and chemokine receptors not always correlate with their functional significance? Why does chemokine antagonism only partially reduce renal leukocyte counts? Will antagonist combinations be more effective in reducing renal inflammation? What are the functional roles of homeostatic chemokines and atypical, nonsignaling chemokine receptors in renal inflammation? And finally, what classes of chemokine antagonists are available to address these questions experimentally?

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“…In neutrophil-mediated mouse models (lipopolysaccharide injection and ischemia-reperfusion injury), deficiency of DARC resulted in a significant reduction in leukocyte recruitment and improved morphology. In particular, the neutrophil recruitment to the post-ischemic kidney was significantly reduced in Darcdeficient mice [30] . We performed unilateral ureteral ligation and nephrotoxic serum nephritis studies in the Darc -deficient mice [31] .…”

Section: Darc In Renal Inflammationmentioning

confidence: 97%

Atypical Chemokine Receptors in Renal Inflammation

Segerer¹,

Jedlička²,

Wüthrich³

2010

Nephron Exp Nephrol

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Chemokines are structurally related proteins which form a large family of chemotactic cytokines. They provide a general communication system for cells and regulate lymphocyte migration. These proteins orchestrate the formation of microenvironments in lymphoid tissue, promote lymphoid organogenesis and help foster vascular and lymphatic angiogenesis. In addition to the classical G proteincoupled chemokine receptors, many chemokines also bind to a family of nonsignaling proteins, now called interceptors (chemokine-internalizing proteins). Here we summarize recent data on the role of interceptors in chemokine biology with a focus on renal inflammation. Atypical Chemokine Receptors in Renal InflammationStephan Segerer a, b Jan Jedlicka a Rudolf P. Wüthrich As inflammatory cells migrate from the bloodstream, a chemokine signal is necessary for firm adhesion to the endothelium of venules. Therefore, chemokines need either to be expressed by endothelial cells, deposited on endothelial surfaces by platelets, or be transported through the endothelial layer, to be presented to passing leukocytes [4] . Having left the vessels, inflammatory cells travel through interstitial tissues most likely following haptotactic (matrix-bound) gradients towards the site of injury [3] . Defined structures of the extracellular matrix, particularly glycosaminoglycans and nonsignaling chemokine-binding proteins, are sites of chemokine presentation, and in the case of the interceptors, also transport [5] . These presenting structures change during inflammation [6] . Additionally, chemokine function is modified by the formation of dimers and multimers, occurring in the ligands and receptors [3] .An additional cascade of interactions between chemokines, soluble mediators, adhesion molecules and chemo- Key WordsChemokines ؒ Chemokine receptors ؒ Interceptors ؒ Nonsignaling receptor ؒ Duffy antigen/receptor for chemokines Abstract Chemokines are structurally related proteins which form a large family of chemotactic cytokines. They provide a general communication system for cells and regulate lymphocyte migration. These proteins orchestrate the formation of microenvironments in lymphoid tissue, promote lymphoid organogenesis and help foster vascular and lymphatic angiogenesis. In addition to the classical G protein-coupled chemokine receptors, many chemokines also bind to a family of nonsignaling proteins, now called interceptors (chemokine-internalizing proteins). Here we summarize recent data on the role of interceptors in chemokine biology with a focus on renal inflammation.

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The Duffy antigen receptor for chemokines in acute renal failure: A facilitator of renal chemokine presentation

Abstract: We suggest that DARC predominantly exerts its effects by controlling spatial chemokine distribution, which in turn regulates neutrophil recruitment and subsequent acute renal failure.

Cited by 41 publications

References 37 publications

The Association Between a Darc Gene Polymorphism and Clinical Outcomes in African American Patients With Acute Lung Injury

The Association Between a Darc Gene Polymorphism and Clinical Outcomes in African American Patients With Acute Lung Injury

Questions about Chemokine and Chemokine Receptor Antagonism in Renal Inflammation

Atypical Chemokine Receptors in Renal Inflammation

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