Platelet Recruitment to the Inflamed Glomerulus Occurs via an αIIbβ3/GPVI-Dependent Pathway

Devi, Sapna; Kuligowski, Michael; Kwan, Rain; Westein, Erik; Jackson, Shaun P.; Kitching, A. Richard; Hickey, Michael J.

doi:10.2353/ajpath.2010.091143

Cited by 64 publications

(68 citation statements)

References 66 publications

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“…A similar implication of neutrophils and GPVI in platelet recruitment to the inflamed vasculature was previously shown in a model of glomerulonephritis induced by IV injection of an antibody to the glomerular basement membrane. 33 Consistent with our results, this previous study showed that neutrophil depletion and GPVI deficiency also reduced platelet accumulation in the inflamed glomerulus. Additionally, our intravital microscopy analysis revealed that neutrophils not only bind platelets directly but also unmask platelet-and GPVI-binding sites on the inflamed vessel wall.…”

Section: Discussionsupporting

confidence: 93%

“…Our results therefore support the concept that the recruitment of platelets and neutrophils to sites of inflamed and/or injured vessels relies on 2-way cooperative interactions. 33,34 In this context, it is interesting to note that the extracellular matrix metalloproteinase inducer (EMMPRIN) was recently identified as a leukocyte counterreceptor for GPVI expressed by neutrophils. 35,36 When addressing the extent of endothelial damage during the early phase of the rpA reaction, we observed that the endothelial lining was generally preserved but displayed alterations in regions of neutrophil infiltration, thus suggesting that endothelial injury and/or endothelial retraction contribute to inflammatory bleeding.…”

Section: Discussionmentioning

confidence: 99%

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Single platelets seal neutrophil-induced vascular breaches via GPVI during immune-complex–mediated inflammation in mice

Gros

Syvannarath

Lamrani

et al. 2015

Blood

156

213

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Key Points• GPVI-dependent platelet binding and activation contribute to seal neutrophilinduced vascular damage in IC-mediated inflammation.• Inflammation represents an uncommon hemostatic situation in which adhesion and activation of single platelets prevent bleeding.Platelets protect vascular integrity during inflammation. Recent evidence suggests that this action is independent of thrombus formation and requires the engagement of glycoprotein VI (GPVI), but it remains unclear how platelets prevent inflammatory bleeding. We investigated whether platelets and GPVI act primarily by preventing detrimental effects of neutrophils using models of immune complex (IC)-mediated inflammation in mice immunodepleted in platelets and/or neutrophils or deficient in GPVI. Depletion of neutrophils prevented bleeding in thrombocytopenic and GPVI 2/2 mice during IC-mediated dermatitis. GPVI deficiency did not modify neutrophil recruitment, which was reduced by thrombocytopenia. Neutrophil cytotoxic activities were reduced in thrombocytopenic and GPVI 2/2 mice during IC-mediated inflammation. Intravital microscopy revealed that in this setting, intravascular binding sites for platelets were exposed by neutrophils, and GPVI supported the recruitment of individual platelets to these spots. Furthermore, the platelet secretory response accompanying IC-mediated inflammation was partly mediated by GPVI, and blocking of GPVI signaling impaired the vasculoprotective action of platelets. Together, our results show that GPVI plays a dual role in inflammation by enhancing neutrophil-damaging activities while supporting the activation and hemostatic adhesion of single platelets to neutrophil-induced vascular breaches. (Blood. 2015;126(8):1017-1026

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Single platelets seal neutrophil-induced vascular breaches via GPVI during immune-complex–mediated inflammation in mice

Gros

Syvannarath

Lamrani

et al. 2015

Blood

156

213

View full text Add to dashboard Cite

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“…In experimental mouse models and patients with different types of glomerulonephritis platelets accumulate in the kidneys and/or platelet-derived factors are systemically elevated (21,22,105–108). Accordingly, some clinical studies (using only a small patient cohort, however) show beneficial effects of anti-platelet therapy in glomerulonephritis patients by reducing circulating platelet aggregates, albuminuria and/or glomerular filtration rate (109–113) and anti-platelet drugs are indeed commonly prescribed in Japanese hospitals to patients with IgA nephropathy (114).…”

Section: Platelet-leukocyte Interactions In Pathologic Conditionsmentioning

confidence: 99%

Measuring and interpreting platelet-leukocyte aggregates

et al. 2018

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Platelets, besides their specialised role in haemostasis and atherothrombosis, actively modulate innate and adaptive immune responses with crucial roles in immune surveillance, inflammation and host defence during infection. An important prerequisite for platelet-mediated changes of immune functions involves direct engagement with different types of leukocytes. Indeed, increased platelet-leukocyte aggregates (PLAs) within the circulation and/or locally at the site of inflammation represent markers of many thrombo-inflammatory diseases, such as cardiovascular diseases, acute lung injury, renal and cerebral inflammation. Therefore, measurement of PLAs could provide an attractive and easily accessible prognostic and/or diagnostic tool for many diseases. To measure PLAs in different (patho-)physiological settings in human and animal models flow cytometric and microscopic approaches have been applied. These techniques represent complementary tools to study different aspects relating to the involvement of leukocyte subtypes and molecules, as well as location of PLAs within tissues, dynamics of their interactions and/or dynamic changes in leukocyte and platelet behaviour. This review summarises various approaches to measure and interpret PLAs and discusses potential experimental factors influencing platelet binding to leukocytes. Furthermore, we summarise insights gained from studies regarding the underlying mechanism of platelet-leukocyte interactions and discuss implications of these interactions in health and disease.

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“…Male mice subjected to unilateral ureteric ligation as previously described (23) were used between 16 and 18 wk of age, 12 wk after undergoing ureteric ligation. For intravital imaging, the posthydronephrotic kidney was prepared as previously described (20,23,42). Briefly, mice were anesthetized by initial i.p.…”

Section: Methodsmentioning

confidence: 99%

Patrolling monocytes promote intravascular neutrophil activation and glomerular injury in the acutely inflamed glomerulus

Finsterbusch

Hall

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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103

141

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Nonclassical monocytes undergo intravascular patrolling in blood vessels, positioning them ideally to coordinate responses to inflammatory stimuli. Under some circumstances, the actions of monocytes have been shown to involve promotion of neutrophil recruitment. However, the mechanisms whereby patrolling monocytes control the actions of neutrophils in the circulation are unclear. Here, we examined the contributions of monocytes to antibody-and neutrophildependent inflammation in a model of in situ immune complexmediated glomerulonephritis. Multiphoton and spinning disk confocal intravital microscopy revealed that monocytes patrol both uninflamed and inflamed glomeruli using β 2 and α 4 integrins and CX 3 CR1. Monocyte depletion reduced glomerular injury, demonstrating that these cells promote inappropriate inflammation in this setting. Monocyte depletion also resulted in reductions in neutrophil recruitment and dwell time in glomerular capillaries and in reactive oxygen species (ROS) generation by neutrophils, suggesting a role for cross-talk between monocytes and neutrophils in induction of glomerulonephritis. Consistent with this hypothesis, patrolling monocytes and neutrophils underwent prolonged interactions in glomerular capillaries, with the duration of these interactions increasing during inflammation. Moreover, neutrophils that interacted with monocytes showed increased retention and a greater propensity for ROS generation in the glomerulus. Also, renal patrolling monocytes, but not neutrophils, produced TNF during inflammation, and TNF inhibition reduced neutrophil dwell time and ROS production, as well as renal injury. These findings show that monocytes and neutrophils undergo interactions within the glomerular microvasculature. Moreover, evidence indicates that, in response to an inflammatory stimulus, these interactions allow monocytes to promote neutrophil recruitment and activation within the glomerular microvasculature, leading to neutrophil-dependent tissue injury.monocyte-neutrophil interaction | inflammation | glomerulonephritis | reactive oxygen species | tumor necrosis factor N eutrophil recruitment is a crucial event in the response to tissue injury and host defense against pathogens. However, if dysregulated, it can also cause significant tissue injury. Inappropriate recruitment and activation of neutrophils are recognized as major contributors to organ damage in numerous inflammatory diseases, including inflammatory arthritis, acute respiratory distress syndrome, systemic lupus erythematosus, and acute glomerulonephritis (1-4). Although our understanding of the molecular basis of neutrophil recruitment is well-developed, less is known about the interactions of neutrophils with other circulating immune cells during the development of the innate inflammatory response. However, over the last decade, evidence has emerged that neutrophil recruitment and function during inflammation can be influenced by another circulating immune cell-the monocyte (5-10).Monocytes exist in two major populations,...

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Platelet Recruitment to the Inflamed Glomerulus Occurs via an αIIbβ3/GPVI-Dependent Pathway

Cited by 64 publications

References 66 publications

Single platelets seal neutrophil-induced vascular breaches via GPVI during immune-complex–mediated inflammation in mice

Single platelets seal neutrophil-induced vascular breaches via GPVI during immune-complex–mediated inflammation in mice

Measuring and interpreting platelet-leukocyte aggregates

Patrolling monocytes promote intravascular neutrophil activation and glomerular injury in the acutely inflamed glomerulus

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