Leukotriene B4, an Inflammatory Mediator in Gout

Rae, S.; Davidson, E. M.; Smith, M. J. H.

doi:10.1016/s0140-6736(82)92785-4

Cited by 183 publications

(63 citation statements)

References 12 publications

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“…The major characteristics of gout include rapid onset, self-limitation, and phagocytosis of the MSU crystals by neutrophils within the synovial cavity, resulting in the release of inflammatory mediators such as leukotriene B 4 , platelet-activating factor, PGE 2 , IL-8, lysosomal proteases, superoxide and a still-unidentified chemotactic factor (11,12,55,56).…”

Section: Discussionmentioning

confidence: 99%

Crystal-Induced Neutrophil Activation: XI. Implication and Novel Roles of Classical Protein Kinase C

Popa-Nita

Proulx

Paré

et al. 2009

The Journal of Immunology

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Monosodium urate (MSU) crystals are among the most potent proinflammatory stimuli, and an innate immune inflammatory response to the crystal surface is involved in the pathology of gouty arthritis. Furthermore, MSU crystals have recently been identified as danger signals able to induce the maturation of dendritic cells. Release of the crystals into the joint cavity promotes an acute inflammation characterized by a massive infiltration of neutrophils that leads to tissue damage. Protein kinase C (PKC) represents a family of serine/threonine kinases that play central signaling roles in multiple cellular responses. This family of kinases is divided into three subfamilies based on second messenger requirements: conventional (or classical), novel, and atypical. Despite their role in signal transduction, very little is known about the involvement of the PKC family in the inflammatory reaction induced by MSU crystals. In the present study, we show that MSU crystals activate conventional PKC isoforms, and that this activation is necessary for the MSU crystal-induced degranulation and generation of a chemotactic activity in the supernatants of MSU crystal-stimulated human neutrophils. Evidence is also obtained that the tyrosine kinase Syk is a substrate of PKC and that the PKC-mediated serine phosphorylation of Syk is necessary to its interaction with the regulatory subunit of PI3K kinases (p85) and thus to the subsequent activation of these lipid kinases. These results suggest novel means of modulating neutrophil responses (through the specific regulation of PKC) during the acute phase of MSU crystal-induced inflammation.

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Section: Discussionmentioning

confidence: 99%

Crystal-Induced Neutrophil Activation: XI. Implication and Novel Roles of Classical Protein Kinase C

Popa-Nita

Proulx

Paré

et al. 2009

The Journal of Immunology

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“…The generation of C5a, kallikrein, bradykinin, and plasmin induces neutrophil chemotaxis and vascular permeability. Urate crystals also induce the production of inflammatory mediators by synovial cells (TNF␣ and IL8) and by neutrophils (LTB4 and IL8) (Matsukawa et al, 1998;Rae et al, 1982). TNF␣ and IL8 induce subsequent production by neutrophils of IL1␤ and IL8, which amplify the leukocyte influx.…”

Section: Iic Crystal-induced Inflammationmentioning

confidence: 99%

Neutrophils: Molecules, Functions and Pathophysiological Aspects

Witko‐Sarsat

Rieu

Descamps‐Latscha

et al. 2000

Laboratory Investigation

951

723

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“…And LTB, is reported to exist in the synovial fluid of patients with rheumatoid arthritis and gout, and in the skin of patients with atopic dermatitis (7)(8)(9). PMN not only show chemotaxis when exposed to LTB4 but they also produce LTB4 when stimulated by chemotactic factors such as C5a, fMLP, PAF, and by the calcium ionophore A23187 (10)(11)(12)(13)(14).…”

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confidence: 99%

Leukotriene B4 Biosynthesis in Polymorphonuclear Leukocytes from Blood of Umbilical Cord, Infants, Children, and Adults

1986

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ABSTRACT. The biosynthesis of 5(S), 12(R)-dihydroxy-6,14-cis-8,lO-trans-eicosatetraenoic acid, leukotriene B4, by human polymorphonuclear leukocytes was examined in relation to age. The leukotriene B4 production by polymorphonuclear leukocytes from unbilical cords, infants, and adults was assayed using high pressure liquid chromatography. The specificity of the leukotriene B4 assay was examined by gas chromatography mass spectrometry. Polymorphonuclear leukocytes from 10 umbilical cords, 24 infants and children, and 10 adults were examined for their ability to synthesize leukotriene B4, in vitro after stimulation by the ionophore A23187 or platelet-activating factor. Among the infants and children, there was a slight agedependent increase of leukotriene B4 production by polymorphonuclear leukocytes in response to ionophore A23187, but it was not statistically significant. Leukotriene B4 production by polymorphonuclear leukocytes in the umbilical cords and infants was not significantly lower than that of polymorphonuclear leukocytes in adults in response to both ionophore A23187 and platelet-activating factor under our experimental conditions. (Pediatr Res 20: 402-406,1986) Abbreviations PMN, polymorphonuclear leukocytes LTB4, leukotriene B4; 5(S),12(R)-dihydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid GC-MS, gas chromatography mass spectrometry PAF, platelet-activating factor fMLP, formyl-methionyl-leucyl-phenylalanine RP-HPLC, reversed phase high pressure liquid chromatography SP-HPLC, straight phase high pressure liquid chromatography RIA, radioimmunoassay SIM, selected ion monitoring 5S,12S-DHETE, 5(S),12(S)-dihydroxy-6,10-trans-8,14-cis-eicosatetraenoic acid PGB, prostaglandin B2 [2H4]PGF2,, tetradeuterated prostaglandin Fza ME-DMiPS, methyl ester dimethylisopropylsilyl

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Leukotriene B4, an Inflammatory Mediator in Gout

Cited by 183 publications

References 12 publications

Crystal-Induced Neutrophil Activation: XI. Implication and Novel Roles of Classical Protein Kinase C

Crystal-Induced Neutrophil Activation: XI. Implication and Novel Roles of Classical Protein Kinase C

Neutrophils: Molecules, Functions and Pathophysiological Aspects

Leukotriene B4 Biosynthesis in Polymorphonuclear Leukocytes from Blood of Umbilical Cord, Infants, Children, and Adults

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