Leukotrienes in Atherosclerosis: New Target Insights and Future Therapy Perspectives

Riccioni, Graziano; Zanasi, Alessandra; Vitulano, Nicola; Malinowska, Barbara; D’Orazio, Nicolantonio

doi:10.1155/2009/737282

Cited by 47 publications

(33 citation statements)

References 60 publications

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“…43,44 It modulates the chemotaxis of DCs from the skin to lymph nodes, 23 the only antigen-presenting cell capable of activating naive T lymphocytes. 3,4 Previous studies aimed at analysing the effect of LTC 4 showed increases in the production of IL-10 by allergen-pulsed DCs, favouring their capacity to increase lung eosinophilia and IL-5 production in a model of murine asthma.…”

Section: Discussionmentioning

confidence: 99%

Leukotriene C4 prevents the complete maturation of murine dendritic cells and modifies interleukin-12/interleukin-23 balance

Álvarez¹,

Amaral²,

Langellotti³

et al. 2011

Immunology

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Summary Leukotriene C4 is an important mediator in the development of inflammatory reactions and ischaemia. Previous studies have shown that leukotriene C4 is able to modulate the function of dendritic cells (DCs) and induce their chemotaxis from skin to lymph node. In this study, we decided to evaluate the modulation exerted by leukotriene C4 on DCs, depending on their status of activation. We showed for the first time that leukotriene C4 stimulates endocytosis both in immature and lipopolysaccharide (LPS) ‐activated DCs. Moreover, it suppressed the interleukin‐12p70 (IL‐12p70) release, but induces the secretion of IL‐23 by DCs activated with LPS and promotes the expansion of T helper type 17 (Th17) lymphocytes. Furthermore, blocking the release of IL‐23 reduced the percentages of CD4+ T cells producing IL‐17 in a mixed lymphocyte reaction. Ours results suggest that leukotriene C4 interferes with the complete maturation of inflammatory DCs in terms of phenotype and antigen uptake, while favouring the release of IL‐23, the main cytokine involved in the maintenance of the Th17 profile.

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Section: Discussionmentioning

confidence: 99%

Leukotriene C4 prevents the complete maturation of murine dendritic cells and modifies interleukin-12/interleukin-23 balance

Álvarez¹,

Amaral²,

Langellotti³

et al. 2011

Immunology

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“…CysLT1 recombinant receptor is activated by all of the native ligands with the following order of potency: LTD4 > LTC4 > LTE4. In contrast, the agonist rank order potency for the CysLT2 receptor is LTD 4 = LTC 4 , with LTE 4 demonstrating less potency [10].…”

Section: Introductionmentioning

confidence: 93%

Leukotrienes Produced in Allergic Lung Inflammation Activate Alveolar Macrophages

Silva

Landgraf²,

Hiyane³

et al. 2010

Cell Physiol Biochem

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It has been well-documented that leukotrienes (LTs) are released in allergic lung inflammation and that they participate in the physiopathology of asthma. A role for LTs in innate immunity has recently emerged: Cys-LTs were shown to enhance FcγR-mediated phagocytosis by alveolar macrophages (AMs). Thus, using a rat model of asthma, we evaluated FcγR-mediated phagocytosis and killing of Klebsiella pneumoniae by AMs. The effect of treatment with a cys-LT antagonist (montelukast) on macrophage function was also investigated. Male Wistar rats were immunized twice with OVA/alumen intraperitoneally and challenged with OVA aerosol. After 24 h, the animals were killed, and the AMs were obtained by bronchoalveolar lavage. Macrophages were cultured with IgG-opsonized red blood cells (50:1) or IgG-opsonized K. pneumoniae (30:1), and phagocytosis or killing was evaluated. Leukotriene C₄ and nitric oxide were quantified by the EIA and Griess methods, respectively. The results showed that AMs from sensitized and challenged rats presented a markedly increased phagocytic capacity via FcγR (10X compared to controls) and enhanced killing of K. pneumoniae (4X higher than controls). The increased phagocytosis was inhibited 15X and killing 3X by treatment of the rats with montelukast, as compared to the non-treated group. cys-LT addition increased phagocytosis in control AMs but had no effect on macrophages from allergic lungs. Montelukast reduced nitric oxide (39%) and LTC₄ (73%). These results suggest that LTs produced during allergic lung inflammation potentiate the capacity of AMs to phagocytose and kill K. pneumonia via FcγR.

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“…Mast cells preform and store approximately 500 secretory granules and many others which are made de novo and are released locally and in systemic circulation when specific antigens react major vasocostricting substance [61]. Leukotrienes are also powerful vasoconstrictors and their biosynthesis is enhanced in the acute phase of unstable angina [62,63]. Thromboxane is a potent mediator of platelet aggregation with vasoconstricting properties [64,65] and PAF, in myocardial ischemia, acts as proadhesive signaling molecule via activation of leukocytes and platelets to release leukotrienes or as a direct vasoconstrictor [66].…”

Section: Pathogenesismentioning

confidence: 99%

Kounis syndrome: an update on epidemiology, pathogenesis, diagnosis and therapeutic management

Kounis¹

2016

Clinical Chemistry and Laboratory Medicine (CCLM)

310

421

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Kounis syndrome has been established as a hypersensitivity coronary disorder induced by various conditions, drugs, environmental exposures, foods and coronary stents. Allergic, hypersensitivity, anaphylactic and anaphylactoid reactions are associated with this syndrome. Vasospastic allergic angina, allergic myocardial infarction and stent thrombosis with occluding thrombus infiltrated by eosinophils and/or mast cells constitute are the three reported, so far, variants of this syndrome. Apart from coronary arteries, it affects the cerebral and mesenteric arteries. Its manifestations are broadening and its etiology is continuously increasing. Kounis syndrome is a ubiquitous disease which represents a magnificent natural paradigm and nature's own experiment in a final trigger pathway implicated in cases of coronary artery spasm and plaque rupture. Kounis syndrome seems to be not a rare disease but an infrequently diagnosed clinical entity which has revealed that the same mediators released from the same inflammatory cells are also present and in acute coronary events of non allergic etiology. These cells are not only present in the culprit region before plaque erosion or rupture but they release their contents just before an actual coronary event. Therefore, awareness of etiology, epidemiology, pathogenesis and clinical manifestations seems to be important for its prognosis, diagnosis, treatment, prevention.

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Leukotrienes in Atherosclerosis: New Target Insights and Future Therapy Perspectives

Cited by 47 publications

References 60 publications

Leukotriene C4 prevents the complete maturation of murine dendritic cells and modifies interleukin-12/interleukin-23 balance

Leukotriene C4 prevents the complete maturation of murine dendritic cells and modifies interleukin-12/interleukin-23 balance

Leukotrienes Produced in Allergic Lung Inflammation Activate Alveolar Macrophages

Kounis syndrome: an update on epidemiology, pathogenesis, diagnosis and therapeutic management

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