Leukotriene B4-Neutrophil Elastase Axis Drives Neutrophil Reverse Transendothelial Cell Migration In Vivo

Colom, Bartomeu; Bodkin, Jennifer V.; Beyrau, Martina; Woodfin, Abigail; Ody, Christiane; Rourke, Colin; Chavakis, Triantafyllos; Brohi, Karim; Imhof, Beat A.; Nourshargh, Sussan

doi:10.1016/j.immuni.2015.05.010

Cited by 209 publications

(274 citation statements)

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“…38,39 Furthermore, S100A9 itself has been shown to attract macrophages 40 ; therefore, S100A9 deposited at the central area of granulomas may serve to recruit macrophages and activate them continuously via receptor for advanced glycation end products and TLR to produce proinflammatory cytokines, such as tumor necrosis factor-a, interleukin-1b, and interleukin-6, as well as chemokines, including macrophage inflammatory protein-1a and monocyte chemoattractant protein-1. 22 The prolonged exposure of macrophages to these highly proinflammatory conditions may lead to their transformation into epithelioid cells and multinucleated giant cells.…”

Section: Discussionmentioning

confidence: 99%

Neutrophils and the S100A9 protein critically regulate granuloma formation

et al. 2016

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Key Points• S100A91 neutrophils accumulated prominently in the central area of granulomas in humans and guinea pigs.• Granuloma formation was markedly impaired by a treatment with the S100A9 inhibitor, tasquinimod. antigen as S100A9, a calcium-binding protein of the S100 family, which was expressed abundantly in neutrophils. Consistent with the multifaceted functions attributed to S100A9, including its role in neutrophil extravasation and macrophage activation, the blockade of S100A9 functions with the specific inhibitor, tasquinimod, impaired the formation of organized granulomas with neutrophil cores. These results demonstrate the critical role of neutrophils and the S100A9 protein in granuloma formation. Because intragranuloma S100A9 1 neutrophils were also detected in humans, these results indicate the potential of tasquinimod, a new anticancer drug candidate, for manipulating human granulomatous diseases.

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Section: Discussionmentioning

confidence: 99%

Neutrophils and the S100A9 protein critically regulate granuloma formation

et al. 2016

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“…On the contrary, excessive LTB4 induced presentation of neutrophil elastase on CD11b, JAM-C degradation, and subsequent reverse transmigration (Figure 2). 27 Neutrophils undergoing reverse transmigration exhibited a proinflammatory phenotype characterized by a high ICAM-1 expression. 28 Interestingly, ICAM-1 high neutrophils were found in distant organs after ischemia/reperfusion or LTB4 infusion, suggesting a potential implication in the systemic propagation of inflammation.…”

Section: Transcriptional Plasticity: Numbers Mattermentioning

confidence: 99%

“…28 Interestingly, ICAM-1 high neutrophils were found in distant organs after ischemia/reperfusion or LTB4 infusion, suggesting a potential implication in the systemic propagation of inflammation. 27,28 Overall, reverse transmigration prolongs neutrophil lifespan and modulates their phenotype and function, thereby contributing to neutrophil heterogeneity.…”

Section: Transcriptional Plasticity: Numbers Mattermentioning

confidence: 99%

Neutrophil heterogeneity: implications for homeostasis and pathogenesis

Silvestre-Roig

Hidalgo

Soehnlein

2016

Blood

359

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Neutrophils are polymorphonuclear leukocytes of the phagocytic system that act as first line of host defense against invading pathogens but are also important mediators of inflammation-induced injury. In contrast to other members of the innate immune system, neutrophils are classically considered a homogenous population of terminally differentiated cells with a well-defined and highly conserved function. Indeed, their short lifespan, the absent proliferative capacity, their limited ability to produce large amounts of cytokines, and the failure to recirculate from the tissue to the bloodstream have sustained this idea. However, increasing evidence over the last decade has demonstrated an unexpected phenotypic heterogeneity and functional versatility of the neutrophil population. Far beyond their antimicrobial functions, neutrophils are emerging as decision-shapers during innate and adaptive immune responses. These emerging discoveries open a new door to understand the role of neutrophils during homeostatic but also pathogenic immune processes. Thus, this review details novel insights of neutrophil phenotypic and functional heterogeneity during homeostasis and disease.

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“…LTB4 binds with high affinity to its G protein-coupled receptor, LTB4R1 (also known as BLT1) (24). After specifically binding to LTB4R1, LTB4 exerts robust effects to promote leukocyte infiltration into various tissues and regulates proinflammatory cytokine production (25)(26)(27)(28)(29). Previous studies have demonstrated effects of the LTB4/LTB4R1 axis on recruitment and activation of macrophages in the context of obesity (30)(31)(32)(33)(34).…”

Section: Introductionmentioning

confidence: 99%