Exosomes Mediate LTB4 Release during Neutrophil Chemotaxis

Majumdar, Ritankar; Tameh, Aidin Tavakoli; Parent, Carole A.

doi:10.1371/journal.pbio.1002336

Cited by 142 publications

(158 citation statements)

References 58 publications

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“…Chemokinecontaining exosomes derived from heat-stressed tumor cells are known to be chemoattractant to dendritic cells. 40 Majumdar et al 21 reported that exosomes secreted from neutrophils synthesize and carry the chemoattractant leukotriene B 4 (LTB4). This LTB4 on exosomes facilitates chemotaxis of neutrophils toward fMLP in both an autocrine and paracrine manner.…”

Section: Resultsmentioning

confidence: 99%

“…20 In neutrophils, autocrine generation of bioactive lipids on exosomes enhances motility toward the chemoattractant N-formyL-MethionyL-LeucyL-Phenylalanine (fMLP). 21 In a previous report, 6 we showed that inhibition of exosome secretion by knockdown of Rab27a, Synaptotagmin7 or Hrs in cancer cells inhibits in vivo metastasis and motility of cancer cells in a chick embryo model system. In this model, exosome secretion controlled both cell speed and directionality; however the directional cues were unclear.…”

Section: Introductionmentioning

confidence: 87%

“…[27][28][29] Recently, exosome secretion was shown to enhance chemotaxis of neutrophils and macrophages. 21,30,31 However, the role of exosome secretion in cancer cell chemotaxis is unknown.…”

Section: Introductionmentioning

confidence: 99%

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Exosome secretion promotes chemotaxis of cancer cells

Sung

Weaver

2017

Cell Adhesion & Migration

102

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Migration of cells toward chemical cues, or chemotaxis, is important for many biologic processes such as immune defense, wound healing and cancer metastasis. Although chemotaxis is thought to occur in cancer cells, it is less well characterized than chemotaxis of professional immune cells such as neutrophils. Here, we show that cancer cell chemotaxis relies on secretion of exosome-type extracellular vesicles. Migration of fibrosarcoma cells toward a gradient of exosome-depleted serum was diminished by knockdown of the exosome secretion regulator Rab27a. Rescue experiments in which chemotaxis chambers were coated with purified extracellular vesicles demonstrate that exosomes but not microvesicles affect both speed and directionality of migrating cells. Chamber coating with purified fibronectin and fibronectin-depleted exosomes demonstrates that the exosome cargo fibronectin promotes cell speed but cannot account for the role of exosomes in promoting directionality of fibrosarcoma cell movement during chemotaxis. These experiments indicate that exosomes contain multiple motility-promoting cargoes that contribute to different aspects of cell motility.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 87%

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Exosome secretion promotes chemotaxis of cancer cells

Sung

Weaver

2017

Cell Adhesion & Migration

102

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“…During the inflammation neutrophils may also contribute to subsequent remodeling. Here, the LTB 4 -induced neutrophil chemotaxis, their released exosomes contain LTB 4 and its synthesizing enzymes [137], and can activate neighboring resting neutrophils in a LTB 4 receptor-dependent manner [138]. Thus, the exosomal pool of LTB 4 acts in an autocrine fashion to sensitize neutrophils towards a primary chemoattractant, and then in a paracrine fashion to mediate recruitment of neighboring neutrophils to augment inflammation.…”

Section: Potential Role Of Exosomes In Airway Remodeling During Latementioning

confidence: 99%

Functions of Exosomes and Microbial Extracellular Vesicles in Allergy and Contact and Delayed-Type Hypersensitivity

Nazimek

Bryniarski²,

Askenase³

2016

Int Arch Allergy Immunol

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Extracellular vesicles, such as exosomes, are newly recognized intercellular conveyors of functional molecular mechanisms. Notably, they transfer RNAs and proteins between different cells that can then participate in the complex pathogenesis of allergic and related hypersensitivity responses and disease mechanisms, as described herein. This review highlights this important new appreciation of the in vivo participation of such extracellular vesicles in the interactions between allergy-mediating cells. We take into account paracrine epigenetic exchanges mediated by surrounding stromal cells and the endocrine receipt of exosomes from distant cells via the circulation. Exosomes are natural ancient nanoparticles of life. They are made by all cells and in some form by all species down to fungi and bacteria, and are present in all fluids. Besides a new focus on their role in the transmission of genetic regulation, exosome transfer of allergens was recently shown to induce allergic inflammation. Importantly, regulatory and tolerogenic exosomes can potently inhibit allergy and hypersensitivity responses, usually acting nonspecifically, but can also proceed in an antigen-specific manner due to the coating of the exosome surface with antibodies. Deep analysis of processes mediated by exosomes should result in the development of early diagnostic biomarkers, as well as allergen-specific, preventive and therapeutic strategies. These will likely significantly diminish the risks of current allergen-specific parenteral desensitization procedures, and of the use of systemic immunosuppressive drugs. Since extracellular vesicles are physiological, they can be fashioned for the specific delivery of therapeutic molecular instructions through easily tolerated, noninvasive routes, such as oral ingestion, nasal administration, and perhaps even inhalation.

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“…Neutrophil migration responds to gradients of exogenous and autocrine/paracrine chemokines (e.g., IL-8), cytokines (e.g., tumor necrosis factor α), as well as bioactive lipids (e.g., leukotriene B 4 (LTB 4 )) [45, 46]. Dynamic expression of specific receptors to these chemokines, cytokines, and bioactive lipids is critical to neutrophil migration.…”

Section: Reviewmentioning

confidence: 99%

Neutrophil plasticity enables the development of pathological microenvironments: implications for cystic fibrosis airway disease

Margaroli

Tirouvanziam

2016

Mol Cell Pediatr

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IntroductionThe pathological course of several chronic inflammatory diseases, including cystic fibrosis, chronic obstructive pulmonary disease, and rheumatoid arthritis, features an aberrant innate immune response dominated by neutrophils. In cystic fibrosis, neutrophil burden and activity of neutrophil elastase in the extracellular fluid have been identified as strong predictors of lung disease severity.ReviewAlthough neutrophils are generally considered to be rigid, pre-programmed effector leukocytes, recent studies suggest extensive plasticity in how neutrophil functions unfold upon recruitment to peripheral tissues, and how they choose their ultimate fate. Indeed, upon migration to cystic fibrosis airways, neutrophils display dysregulated lifespan, metabolic activation, and altered effector and regulatory functions, consistent with profound adaptation and phenotypic reprogramming. Licensed by signals present in cystic fibrosis airway microenvironment to survive and develop these novel functions, neutrophils orchestrate, in partnership with the epithelium and with the resident microbiota, the evolution of a pathological microenvironment. This microenvironment is defined by altered proteolytic, redox, and metabolic balance and the presence of stable luminal structures in which neutrophils and microbes coexist.ConclusionsThe elucidation of molecular mechanisms driving neutrophil plasticity in vivo will open new treatment opportunities designed to modulate, rather than block, the crucial adaptive functions fulfilled by neutrophils. This review aims to outline emerging mechanisms of neutrophil plasticity and their participation in the building of pathological microenvironments in the context of cystic fibrosis and other diseases with similar features.

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Exosomes Mediate LTB4 Release during Neutrophil Chemotaxis

Cited by 142 publications

References 58 publications

Exosome secretion promotes chemotaxis of cancer cells

Exosome secretion promotes chemotaxis of cancer cells

Functions of Exosomes and Microbial Extracellular Vesicles in Allergy and Contact and Delayed-Type Hypersensitivity

Neutrophil plasticity enables the development of pathological microenvironments: implications for cystic fibrosis airway disease

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