Lipoxin A4 Attenuates Microvascular Fluid Leak During Inflammation

Ereso, Alexander Q.; Cureton, Elizabeth L.; Cripps, Michael W.; Sadjadi, Javid; Dua, Monica M.; Curran, Brian; Victorino, Gregory P.

doi:10.1016/j.jss.2009.01.009

Cited by 16 publications

(14 citation statements)

References 34 publications

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“…The specific interaction of the pro-resolution mediators with G protein-coupled receptors (GPCR 32, ALX, BLT1) on the surface of immune cells induces a number of pro-resolution processes. For instance, leukocyte migration is reduced [194], vascular permeability returns to normal [195], pro-inflammatory neutrophils undergo apoptosis [196] and M2 macrophages phagocytose apoptotic neutrophils, bacterial remnants and necrotic debris [197]. While adequate inflammatory resolution prevents tissue injury leading to restitutio ad integrum , inadequate resolution results in chronic inflammation.…”

Section: Biological Function Of Mammalian Lox Isoformsmentioning

confidence: 99%

Mammalian lipoxygenases and their biological relevance

Kühn

Banthiya

Leyen

2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

468

431

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Lipoxygenases (LOXs) form a heterogeneous class of lipid peroxidizing enzymes, which have been implicated in cell proliferation and differentiation but also in the pathogenesis of various diseases with major public health relevance. As other fatty acid dioxygenases LOX oxidize polyunsaturated fatty acids to their corresponding hydroperoxy derivatives, which are further transformed to bioactive lipid mediators (eicosanoids and related substances). On the other hand, lipoxygenases are key players in regulation of the cellular redox homeostasis, which is an important element in gene expression regulation. Although the first mammalian lipoxygenases were discovered 40 years ago and although the enzymes have been well characterized with respect to their structural and functional properties the biological roles of the different lipoxygenase isoforms are not completely understood. This review is aimed at summarizing the current knowledge on the physiological roles of different mammalian LOX-isoforms and their patho-physiological function in inflammatory, metabolic, hyperproliferative, neurodegenerative and infectious disorders.

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Section: Biological Function Of Mammalian Lox Isoformsmentioning

confidence: 99%

Mammalian lipoxygenases and their biological relevance

Kühn

Banthiya

Leyen

2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

468

431

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“…This is supported by the observation that lipopolysaccharide (LPS) or platelet activating factor (PAF)-induced intravascular volume loss (microvascular fluid leak) was attenuated by LXA 4 [47]. In a cecal ligation and puncture (CLP) model of sepsis, when LXA 4 (40 µg/kg, i.p .)…”

Section: Sepsis As a Pro-resolution Deficiency Disordermentioning

confidence: 99%

State of the art papers HLA-DR expression, cytokines and bioactive lipids in sepsis

Das¹

2014

aoms

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Sepsis accounts for more than 200,000 deaths annually in the USA alone. Both inflammatory and anti-inflammatory responses occur simultaneously in sepsis, the early phase dominated by the hyperinflammatory response and the late phase by immunosuppression. This late immunosuppression phase leads to loss of the delayed type hypersensitivity response, failure to clear the primary infection and development of secondary infections. Based on the available data, I hypothesize that failure to produce adequate amounts of inflammation resolving lipid mediators may be at the centre of both the hyperinflammatory response and late immunosuppression seen in sepsis. These proresolving lipids – lipoxins, resolvins and protectins – suppress exacerbated activation of leukocytes and macrophages, inhibit excess production of pro-inflammatory cytokines, initiate resolution of inappropriate inflammation, augment clearance of bacteria and other pathogens, and restore homeostasis. If true, this implies that administration of naturally occurring lipoxins, resolvins, protectins, maresins and nitrolipids by themselves or their more stable synthetic analogues such as 15-epi-16-(para-fluorophenoxy)-lipoxin A4-methyl ester, a synthetic analogue of 15-epi-lipoxin A4, and 15(R/S)-methyl-LXA4 may form a new approach in the prevention (in the high-risk subjects), management of sepsis and in resolving the imbalanced inflammatory process such that sepsis is ameliorated early. In addition, recent studies have suggested that nociceptin and cold inducible RNA binding protein (CIRBP) also have a role in the pathobiology of sepsis. It is suggested that both nociceptin and CIRBP inhibit the production of lipoxins, resolvins, protectins, maresins, and nitrolipids and thus play a role in sepsis and septic shock.

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“…43 Furthermore, LXA 4 reduces microvascular permeability in inflammatory rat mesenteric arteries, supporting its proresolution properties. 44 In a randomized human trial 45 of healthy patients who received aspirin or placebo, platelet reactivity, as assessed by plasma thromboxane B 2 levels, was inversely related to plasma ATL concentration, which might account for the anti-inflammatory and antineutrophil actions of aspirin. In neutrophils, myeloperoxidase suppresses the apoptotic process via modulation of Mac-1 signaling, thereby prolonging inflammation.…”

Section: Bioactive Lipid Mediators In the Resolution Of Inflammationmentioning

confidence: 99%

Mechanisms of Resolution of Inflammation

Maskrey

Megson

Whitfield

et al. 2011

ATVB

151

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Abstract-The inflammatory response is an integral part of the innate immune mechanism that is triggered in response to a real or perceived threat to tissue homeostasis, with a primary aim of neutralizing infectious agents and initiating repair to damaged tissue. By design, inflammation is a finite process that resolves as soon as the threat of infection abates and sufficient repair to the tissue is complete. Resolution of inflammation involves apoptosis and subsequent clearance of activated inflammatory cells -a tightly regulated event. Chronic inflammation is a characteristic feature in virtually all inflammatory diseases, including atherosclerosis, and it is becoming increasingly clear that derangement of the processes usually involved in resolution of inflammation is an underlying feature of chronic inflammatory conditions. This review will draw on evidence from a range of diseases in which dysregulated inflammation is important, with particular emphasis on cardiovascular disease. (Arterioscler Thromb Vasc Biol. 2011;31:1001-1006.)Key Words: atherosclerosis Ⅲ eicosanoids Ⅲ lipids Ⅲ NO Ⅲ resolution of inflammation I nflammation is a primary component of the immune system that is triggered by any stimulus that poses a real or perceived threat to tissue homeostasis. 1 The acute inflammatory process is characterized by rapid recruitment of granulocytes (ie, neutrophils, eosinophils, and basophils) to the inflammatory site; the relative contribution of these cell types is dependent on the location of the inflammatory site in question. The migration of granulocytes to inflammatory loci is a necessary requirement for the neutralization and removal of deleterious agents; these cells play a key role in the defense against bacterial, fungal, and viral infections and in resistance to parasitic invasion and the allergic response. Resolution of inflammation is perceived to occur by elimination of granulocytes and the eventual return of tissue mononuclear cell (macrophage and lymphocyte) numbers to basal levels. 2 For effective resolution to occur, cessation of proinflammatory signaling is a prerequisite that pre-empts removal of infiltrating granulocytes. During spontaneous resolution, neutrophils undergo apoptosis, a highly regulated cell death mechanism that prevents the release of histotoxic cellular contents. 3 Alterations in neutrophil cell surface markers and morphological changes during apoptosis correlate with increased recognition by professional phagocytes, such as macrophages, that mediate effective clearance of dying cells. 3,4 It is accepted that the resolution process is active, rather than passive, and is controlled by a range of tightly regulated biochemical and cellular mechanisms. 2 The acute inflammatory response is self-limiting and normally results in tissue restoration and the return of tissue homeostasis. Persistent inflammatory stimuli or dysregulation of mechanisms of the resolution phase results in chronic inflammation, 2 recognized to be a key underlying factor in the progression of a range of d...

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Lipoxin A4 Attenuates Microvascular Fluid Leak During Inflammation

Cited by 16 publications

References 34 publications

Mammalian lipoxygenases and their biological relevance

Mammalian lipoxygenases and their biological relevance

State of the art papers HLA-DR expression, cytokines and bioactive lipids in sepsis

Mechanisms of Resolution of Inflammation

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