共查询到20条相似文献,搜索用时 15 毫秒
1.
Jaramillo M Naccache PH Olivier M 《Journal of immunology (Baltimore, Md. : 1950)》2004,172(9):5734-5742
Elevated NO production has been detected in patients suffering from various arthropathies; however, its role and regulation during gouty arthritis remain largely unexplored. Monosodium urate (MSU) crystals, the causative agent of gout, have been shown to induce NO generation in vivo and inducible NO synthase (iNOS) expression in human monocytes. The present study was designed to evaluate the ability of MSU crystals to modulate macrophage (M phi) iNOS expression and NO synthesis and to investigate the molecular mechanisms underlying these cellular responses. We found that MSU crystals did not induce NO production in murine J774 M phi. However, a synergistic effect on the level of iNOS expression and NO generation was observed in cells exposed to MSU crystals in combination with IFN-gamma. Characterization of the second messengers involved revealed the requirement of IFN-gamma-mediated Janus kinase 2/STAT1 alpha activation even though MSU crystals did not modulate this signaling cascade by themselves. MSU crystals exerted their up-regulating effect by increasing extracellular signal-regulated kinase (ERK) 1/2 phosphorylation and NF-kappa B nuclear translocation in response to IFN-gamma. The use of specific inhibitors against either NF-kappa B or the ERK1/2 pathway significantly reduced MSU + IFN-gamma-inducible NF-kappa B activity, iNOS expression, and NO production. Altogether, these data indicate that MSU crystals exert a potent synergistic effect on the IFN-gamma-inducible M phi NO generation via ERK1/2- and NF-kappa B-dependent pathways. Understanding the molecular mechanisms through which MSU crystals amplify M phi responses to proinflammatory cytokines such as IFN-gamma will contribute to better define their role in NO regulation during gout, in particular, and inflammation, in general. 相似文献
2.
Signaling events involved in macrophage chemokine expression in response to monosodium urate crystals 总被引:5,自引:0,他引:5
Jaramillo M Godbout M Naccache PH Olivier M 《The Journal of biological chemistry》2004,279(50):52797-52805
3.
TLR2 signaling in chondrocytes drives calcium pyrophosphate dihydrate and monosodium urate crystal-induced nitric oxide generation 总被引:4,自引:0,他引:4
Liu-Bryan R Pritzker K Firestein GS Terkeltaub R 《Journal of immunology (Baltimore, Md. : 1950)》2005,174(8):5016-5023
Microcrystals of calcium pyrophosphate dihydrate (CPPD) and monosodium urate (MSU) deposited in synovium and articular cartilage initiate joint inflammation and cartilage degradation in large part by binding and directly activating resident cells. TLRs trigger innate host defense responses to infectious pathogens, and the expression of certain TLRs by synovial fibroblasts has revealed the potential for innate immune responses to be triggered by mesenchymally derived resident cells in the joint. In this study we tested the hypothesis that chondrocytes also express TLRs and that one or more TLRs centrally mediate chondrocyte responsiveness to CPPD and MSU crystals in vitro. We detected TLR2 expression in normal articular chondrocytes and up-regulation of TLR2 in osteoarthritic cartilage chondrocytes in situ. We demonstrated that transient transfection of TLR2 signaling-negative regulator Toll-interacting protein or treatment with TLR2-blocking Ab suppressed CPPD and MSU crystal-induced chondrocyte release of NO, an inflammatory mediator that promotes cartilage degeneration. Conversely, gain-of-function of TLR2 in normal chondrocytes via transfection was associated with increased CPPD and MSU crystal-induced NO release. Canonical TLR signaling by parallel pathways involving MyD88, IL-1R-associated kinase 1, TNF receptor-associated factor 6, and IkappaB kinase and Rac1, PI3K, and Akt critically mediated NO release in chondrocytes stimulated by both CPPD and MSU crystals. We conclude that CPPD and MSU crystals critically use TLR2-mediated signaling in chondrocytes to trigger NO generation. Our results indicate the potential for innate immunity at the level of the articular chondrocyte to directly contribute to inflammatory and degenerative tissue reactions associated with both gout and pseudogout. 相似文献
4.
Interleukin 1 (IL 1) as a mediator of crystal arthritis. Stimulation of T cell and synovial fibroblast mitogenesis by urate crystal-induced IL 1 总被引:14,自引:0,他引:14
F S Di Giovine S E Malawista G Nuki G W Duff 《Journal of immunology (Baltimore, Md. : 1950)》1987,138(10):3213-3218
We reported before that monosodium urate (MSU) crystals were potent stimulators of endogenous pyrogen (EP) production from human and rabbit mononuclear phagocytes, and proposed that this property of MSU crystals may be important in the pathogenesis of gout. EP activity is now attributed to interleukin 1 (IL 1) peptides but IL 1 is not the only pyrogenic monocyte-derived cytokine, since both interferon-alpha (alpha-IFN) and tumor necrosis factor (TNF) are also pyrogenic in rabbits. Using a T cell comitogenic assay based on a murine helper T cell clone that does not respond to IFN or TNF, we now report the release of IL 1 activity from human blood monocytes and synovial fluid mononuclear cells (MNC), following stimulation with MSU crystals. MSU-induced supernatants with IL 1 activity were neutralized with rabbit antiserum to human IL 1 and also stimulated the growth ([3H]thymidine incorporation) of long-term fibroblast-like cell lines derived from human synovial rheumatoid exudate. Two other crystals associated with articular inflammation were tested: hydroxyapatite was a much less potent stimulus compared with MSU crystals, and calcium pyrophosphate dihydrate did not stimulate IL 1 release from human monocytes or synovial fluid MNC. As a model for the inflammatory consequences of acute and chronic overproduction of IL 1, gout is the only sterile inflammatory disease where the local and systemic pathology is compatible with such overproduction; raised IL 1 levels have been found at the site of inflammation, and a necessary etiologic agent, crystalline urate, has been shown unequivocally to be a direct activator of mononuclear IL 1 release. 相似文献
5.
BACKGROUND The diagnosis of gout can be problematic when the presentation is atypical and serum uric acid is borderline elevated. Demonstration of monosodium urate (MSU) crystals in fine needle aspiration (FNA) smears from nodular masses clinically suspected to be tophi establishes the diagnosis unequivocally. CASES: Of the 7 cases in this study, 4 were suspected clinically to have gouty tophi. Giant cell tumor of tendon sheath, giant cell tumor of bone and metastatic tumor with multicentric involvement of bone were the clinical diagnoses in 1 case each. Serum uric acid levels high enough to be in the diagnostic range for gout were reported in 3 cases, within normal limits in 3 cases and low in 1 chronic alcoholic patient. Bright field microscopy of FNA smears revealed singly scattered or stacks of MSU crystals with variable number of inflammatory cells, with or without foreign body giant cells in 6 cases. In 1 patient, FNA showed stacks of MSU crystals only. Characteristic birefringence of MSU crystals was observed on polarizing microscopy. CONCLUSION: FNA demonstration of MSU crystals on polarizing microscopy can easily establish the nature of the nodules in and around the joints and in soft tissue as gouty tophi and is thus an investigation differentiating this lesion from other masses clinically simulating it. 相似文献
6.
So A 《Arthritis research & therapy》2008,10(5):221
Gout is the most common form of inflammatory arthritis in the elderly. In the last two decades, both hyperuricemia and gout
have increased markedly and similar trends in the epidemiology of the metabolic syndrome have been observed. Recent studies
provide new insights into the transporters that handle uric acid in the kidney as well as possible links between these transporters,
hyperuricemia, and hypertension. The treatment of established hyperuricemia has also seen new developments. Febuxostat and
PEG-uricase are two novel treatments that have been evaluated and shown to be highly effective in the management of hyperuricemia,
thus enlarging the therapeutic options available to lower uric acid levels. Monosodium urate (MSU) crystals are potent inducers
of inflammation. Within the joint, they trigger a local inflammatory reaction, neutrophil recruitment, and the production
of pro-inflammatory cytokines as well as other inflammatory mediators. Experimentally, the uptake of MSU crystals by monocytes
involves interactions with components of the innate immune system, namely Toll-like receptor (TLR)-2, TLR-4, and CD14. Intracellularly,
MSU crystals activate multiple processes that lead to the formation of the NALP-3 (NACHT, LRR, and pyrin domain-containing-3)
inflammasome complex that in turn processes pro-interleukin (IL)-1 to yield mature IL-1β, which is then secreted. The inflammatory
effects of MSU are IL-1-dependent and can be blocked by IL-1 inhibitors. These advances in the understanding of hyperuricemia
and gout provide new therapeutic targets for the future. 相似文献
7.
BACKGROUND: The definitive diagnosis of gout is best established by demonstration of monosodium urate (MSU) crystals in the synovial fluid or biopsy. Fine needle aspiration cytology (FNAC) of tophi can play a crucial role in diagnosis. CASES: A 36-year-old chronic alcoholic male developed subcutaneous nodules on both malleoli without a history of arthropathy and with normal serum uric acid levels. FNAC of the nodules demonstrated stacks and sheaves of needle-shaped crystals of MSU. A 50-year-old diabetic male developed multiple nodules on the feet. He gave a past history of painful athropathy. A roentgenogram of the feet was suspicious for gout; however, joint aspiration failed, and the serum uric acid levels were normal. At this juncture FNAC of the feet tophi clinched the diagnosis of gout. In both cases, polarization of needle washings (wet mount) and the fixed, Papanicolaoustained smears showed negatively birefringent, needle-shaped crystals of MSU, thus confirming the diagnosis of gout. CONCLUSION: FNAC of gouty tophi is an easy alternative to synovial biopsy and joint fluid analysis. It is simpler, easier and less painful. As crystals are preserved in stained smears, they can be employed for polarization and confirmation of gout. 相似文献
8.
Lauri J. Moilanen Mari H?m?l?inen Lauri Lehtim?ki Riina M. Nieminen Eeva Moilanen 《PloS one》2015,10(2)
IntroductionIn gout, monosodium urate (MSU) crystals deposit intra-articularly and cause painful arthritis. In the present study we tested the hypothesis that Transient Receptor Poten-tial Ankyrin 1 (TRPA1), an ion channel mediating nociceptive signals and neurogenic in-flammation, is involved in MSU crystal-induced responses in gout by utilizing three experi-mental murine models.MethodsThe effects of selective pharmacological inhibition (by HC-030031) and genetic depletion of TRPA1 were studied in MSU crystal-induced inflammation and pain by using 1) spontaneous weight-bearing test to assess MSU crystal-induced joint pain, 2) subcutaneous air-pouch model resembling joint inflammation to measure MSU crystal-induced cytokine production and inflammatory cell accumulation, and 3) MSU crystal-induced paw edema to assess acute vascular inflammatory responses and swelling.ResultsIntra-articularly injected MSU crystals provoked spontaneous weight shift off from the affected limb in wild type but not in TRPA1 knock-out mice referring alleviated joint pain in TRPA1 deficient animals. MSU crystal-induced inflammatory cell infiltration and accumulation of cytokines MCP-1, IL-6, IL-1beta, MPO, MIP-1alpha and MIP-2 into subcu-taneous air-pouch (resembling joint cavity) was attenuated in TRPA1 deficient mice and in mice treated with the selective TRPA1 inhibitor HC-030031 as compared to control animals. Further, HC-030031 treated and TRPA1 deficient mice developed tempered inflammatory edema when MSU crystals were injected into the paw.ConclusionsTRPA1 mediates MSU crystal-induced inflammation and pain in experimental models supporting the role of TRPA1 as a potential mediator and a drug target in gout flare. 相似文献
9.
P2Y6 receptor signaling pathway mediates inflammatory responses induced by monosodium urate crystals
Uratsuji H Tada Y Kawashima T Kamata M Hau CS Asano Y Sugaya M Kadono T Asahina A Sato S Tamaki K 《Journal of immunology (Baltimore, Md. : 1950)》2012,188(1):436-444
Gout occurs in individuals with hyperuricemia when monosodium urate (MSU) crystals precipitate in tissues and induce acute inflammation via phagocytic cells such as monocytes. MSU crystals have been demonstrated in skin diseases such as tophaceous gout or psoriasis; however, the importance of MSU crystals in the skin is totally unknown. In this study, we found that MSU crystals, through P2Y(6) receptors, stimulated normal human keratinocytes (NHK) to produce IL-1α, IL-8/CXCL8, and IL-6. P2Y(6) receptor expression increased in MSU-stimulated NHK. Both P2Y(6)-specific antagonist and P2Y(6) antisense oligonucleotides significantly inhibited the production of IL-1α, IL-8/CXCL8, and IL-6 by NHK. Similarly, the P2Y(6)-specific antagonist completely inhibited the MSU-induced production of IL-1β by THP-1 cells, a human monocytic cell line. Remarkably, the P2Y(6)-specific antagonist significantly reduced neutrophil influx in both mouse air pouch and peritonitis models. Thus, these results indicate that the P2Y(6) receptor signaling pathway may be a potential therapeutic target for MSU-associated inflammatory diseases, such as tophaceous gout. 相似文献
10.
Gouty arthritis is a characteristically intense acute inflammatory reaction that erupts in response to articular deposits of monosodium urate (MSU) crystals. Important recent molecular biologic advances in this field have given us a clear picture of the mechanistic basis of gouty inflammation. The innate immune inflammatory response is critically involved in the pathology of gout. Specifically, MSU crystals promote inflammation directly by stimulating cells via Toll-like receptor signaling and by providing a surface for cleavage of C5 and formation of complement membrane attack complex (C5b-9), culminating in secretion of cytokines, chemokines, and other inflammatory mediators with a dramatic influx of neutrophils into the joint. Despite the detailed mechanistic picture for gouty inflammation, there are no placebo-controlled, randomized clinical studies for any of the therapies commonly used, although comparative studies have demonstrated that many nonsteroidal anti-inflammatory drugs are equivalent to indomethacin with respect to controlling acute gouty attacks. In general, the first line of anti-inflammatory therapy for acute gout is nonsteroidal anti-inflammatory drugs, and the selective cyclo-oxygenase-2 inhibitor celecoxib can be used where appropriate. The second line of treatment is glucocorticosteroids, given systemically (oral, intravenous, or intramuscular) or intra-articularly. Alternatively, synthetic adrenocorticotropic hormone is effective, partly via induction of adrenal glucocorticosteroids and partly via rapid peripheral suppression of leukocyte activation by melatonin receptor 3 signaling. The third line of treatment is oral colchicine, which is highly effective when given early in an acute gouty attack, but it is poorly tolerated because of predictable gastrointestinal side effects. 相似文献
11.
Acute gout attacks produce severe joint pain and inflammation associated with monosodium urate (MSU) crystals leading to oxidative stress production. The transient potential receptor ankyrin 1 (TRPA1) is expressed by a subpopulation of peptidergic nociceptors and, via its activation by endogenous reactive oxygen species, including hydrogen peroxide (H2O2), contributes to pain and neurogenic inflammation. The aim of this study was to investigate the role of TRPA1 in hyperalgesia and inflammation in a model of acute gout attack in rodents. Inflammatory parameters and mechanical hyperalgesia were measured in male Wistar rats and in wild-type (Trpa1+/+) or TRPA1-deficient (Trpa1−/−) male mice. Animals received intra-articular (ia, ankle) injection of MSU. The role of TRPA1 was assessed by receptor antagonism, gene deletion or expression, sensory fiber defunctionalization, and calcitonin gene-related peptide (CGRP) release. We found that nociceptor defunctionalization, TRPA1 antagonist treatment (via ia or oral administration), and Trpa1 gene ablation abated hyperalgesia and inflammatory responses (edema, H2O2 generation, interleukin-1β release, and neutrophil infiltration) induced by ia MSU injection. In addition, we showed that MSU evoked generation of H2O2 in synovial tissue, which stimulated TRPA1 producing CGRP release and plasma protein extravasation. The MSU-elicited responses were also reduced by the H2O2-detoxifying enzyme catalase and the reducing agent dithiothreitol. TRPA1 activation by MSU challenge-generated H2O2 mediates the entire inflammatory response in an acute gout attack rodent model, thus strengthening the role of the TRPA1 receptor and H2O2 production as potential targets for treatment of acute gout attacks. 相似文献
12.
Pessler F Mayer CT Jung SM Behrens EM Dai L Menetski JP Schumacher HR 《Arthritis research & therapy》2008,10(3):R64
Introduction
The murine air pouch is a bursa-like space that resembles the human synovial membrane. Injection of monosodium urate (MSU) crystals into the pouch elicits an acute inflammatory response similar to human gout. We conducted the present study to identify mRNAs that were highly regulated by MSU crystals in the pouch membrane. 相似文献13.
14.
A structural approach to pathological crystallizations. Gout: the possible role of albumin in sodium urate crystallization 总被引:2,自引:0,他引:2
D Perl-Treves L Addadi 《Proceedings of the Royal Society of London. Series B, Containing papers of a Biological character. Royal Society (Great Britain)》1988,235(1279):145-159
The interactions between sodium urate monohydrate (MSU) crystals and human serum albumin (HSA) were investigated in vitro in relation to the disease of gout. It was found that HSA accelerates (by up to ten times or even more) the nucleation of MSU crystals at a pH of more than 7.5, but only to a much lesser extent (1.2 times) at pH 7.0. Protein denaturation, as well as blocking exposed carboxylate groups on the protein, substantially reduced the nucleating effect. By use of immunofluorescence, immunogold labelling and crystal morphology studies, albumin was shown to interact preferentially with the (110) faces of MSU crystals. Taking these results into consideration, a mechanism is proposed whereby albumin stabilizes MSU crystal nuclei by interaction of structured carboxylate-containing protein domains with planes of the incipient crystal exposing sodium cation layers. 相似文献
15.
Mitroulis I Kambas K Chrysanthopoulou A Skendros P Apostolidou E Kourtzelis I Drosos GI Boumpas DT Ritis K 《PloS one》2011,6(12):e29318
Background
Gout is a prevalent inflammatory arthritis affecting 1–2% of adults characterized by activation of innate immune cells by monosodium urate (MSU) crystals resulting in the secretion of interleukin-1β (IL-1β). Since neutrophils play a major role in gout we sought to determine whether their activation may involve the formation of proinflammatory neutrophil extracellular traps (NETs) in relation to autophagy and IL-1β.Methodology/Principal Findings
Synovial fluid neutrophils from six patients with gout crisis and peripheral blood neutrophils from six patients with acute gout and six control subjects were isolated. MSU crystals, as well as synovial fluid or serum obtained from patients with acute gout, were used for the treatment of control neutrophils. NET formation was assessed using immunofluorescence microscopy. MSU crystals or synovial fluid or serum from patients induced NET formation in control neutrophils. Importantly, NET production was observed in neutrophils isolated from synovial fluid or peripheral blood from patients with acute gout. NETs contained the alarmin high mobility group box 1 (HMGB1) supporting their pro-inflammatory potential. Inhibition of phosphatidylinositol 3-kinase signaling or phagolysosomal fusion prevented NET formation, implicating autophagy in this process. NET formation was driven at least in part by IL-1β as demonstrated by experiments involving IL-1β and its inhibitor anakinra.Conclusions/Significance
These findings document for the first time that activation of neutrophils in gout is associated with the formation of proinflammatory NETs and links this process to both autophagy and IL-1β. Modulation of the autophagic machinery may represent an additional therapeutic study in crystalline arthritides. 相似文献16.
17.
Humaira Rasheed Cushla McKinney Lisa K. Stamp Nicola Dalbeth Ruth K. Topless Richard Day Diluk Kannangara Kenneth Williams Malcolm Smith Matthijs Janssen Tim L. Jansen Leo A. Joosten Timothy R. Radstake Philip L. Riches Anne-Kathrin Tausche Frederic Lioté Leo Lu Eli A. Stahl Hyon K. Choi Alexander So Tony R. Merriman 《PloS one》2016,11(1)
Deposition of crystallized monosodium urate (MSU) in joints as a result of hyperuricemia is a central risk factor for gout. However other factors must exist that control the progression from hyperuricaemia to gout. A previous genetic association study has implicated the toll-like receptor 4 (TLR4) which activates the NLRP3 inflammasome via the nuclear factor-κB signaling pathway upon stimulation by MSU crystals. The T-allele of single nucleotide polymorphism rs2149356 in TLR4 is a risk factor associated with gout in a Chinese study. Our aim was to replicate this observation in participants of European and New Zealand Polynesian (Māori and Pacific) ancestry. A total of 2250 clinically-ascertained prevalent gout cases and 13925 controls were used. Non-clinically-ascertained incident gout cases and controls from the Health Professional Follow-up (HPFS) and Nurses Health Studies (NHS) were also used. Genotypes were derived from genome-wide genotype data or directly obtained using Taqman. Logistic regression analysis was done including age, sex, diuretic exposure and ancestry as covariates as appropriate. The T-allele increased the risk of gout in the clinically-ascertained European samples (OR = 1.12, P = 0.012) and decreased the risk of gout in Polynesians (OR = 0.80, P = 0.011). There was no evidence for association in the HPFS or NHS sample sets. In conclusion TLR4 SNP rs2143956 associates with gout risk in prevalent clinically-ascertained gout in Europeans, in a direction consistent with previously published results in Han Chinese. However, with an opposite direction of association in Polynesians and no evidence for association in a non-clinically-ascertained incident gout cohort this variant should be analysed in other international gout genetic data sets to determine if there is genuine evidence for association. 相似文献
18.
Alexander So 《Arthritis research & therapy》2013,15(5):118
Most research in gout has concentrated on the proinflammatory mechanisms to
explain the inflammation that is generated when leucocytes are in contact with
monosodium urate crystals. However, the episodic nature of gout and the absence
of inflammation even when crystals are present suggest that there are natural
counter-regulatory mechanisms to limit the inflammatory response. Gagné and
colleagues showed that myeloid inhibitory C-type lectin, a C-type lectin
inhibitory receptor expressed on neutrophils, modulates monosodium urate-induced
neutrophil responses in vitro.Neutrophil recruitment and activation play a key role in the acute inflammatory
response to monosodium urate (MSU) crystals. In acute gout, our current treatments
such as nonsteroidal anti-inflammatory drugs, colchicine or corticosteroids all act
on different steps of neutrophil activation. These drugs form part of the first
treatment objective in gout – to relieve the painful symptoms of the acute
attack – but do not address the second objective, which is to treat the
underlying metabolic disorder hyperuricemia. Can neutrophil activation be
manipulated or regulated? Are there signals that can be modulated and can this be of
clinical relevance?The article by Gagné and colleagues provides evidence for an inhibitory pathway
of neutrophil activation that acts through a recently described C-type lectin
receptor called the myeloid inhibitory C-type lectin (MICL) [1]. This membrane receptor, also known as CLEC12A, inhibits neutrophil
activation when it is engaged. C-type lectin receptors form a large family of
proteins that have a common type of carbohydrate-binding domain that mediate cell
adhesion and ligand binding in a calcium-dependent manner. Members of the C-type
lectin receptors are known to participate in immune regulation, with well-known
examples including Dectin-1 (CLE7A), DC-sign (CD209 or CLEC4L) and natural killer
cell receptors (Ly49 or KLRA1). The MICL protein is encoded on chromosome 12p13,
closely linked to the natural killer gene complex. MICL contains a cytoplasmic
immunoreceptor tyrosine-based inhibitory motif and is expressed mainly on
neutrophils and monocytes. Previous work has shown that the receptor could inhibit
cellular activation [2]. The ligands that lead to MICL activation are currently unknown, as there
is only a small body of data to show that the receptor interacts with ligands
expressed in the bone marrow, thymus and kidney [3].In their studies, Gagné and colleagues showed that MSU crystals as well as a
MICL-specific antibody downmodulated MICL expression on neutrophils. Reducing the
expression of MICL by transfecting small interfering RNA or by antibody modulation
of the receptor led to enhanced production of IL-8 when MSU was added to
neutrophils, but no changes in IL-1β secretion were observed. The mechanisms of
MICL signaling probably involve tyrosine phosphorylation as well as calcium flux,
differing from previous results that showed MICL associated with the phosphatases
SHP-1 and SHP-2 [2]. Finally, the addition of colchicine to neutrophils abrogated the
negative effect of MSU on MICL expression.These results showed that reduced MICL expression is associated with augmented
inflammatory responses from neutrophils, and a higher level of neutrophil MICL
expression is associated with a reduced IL-8 production in vitro. As IL-8
is a major neutrophil chemoattractant, this can have important effects on neutrophil
recruitment to an inflammatory site in gout. By extrapolation, if MICL expression or
signaling could be enhanced or maintained during inflammation, the inhibitory signal
may be reinforced and thereby downregulate inflammation. The effect of colchicine in
this system is to elevate the expression of MICL, thereby increasing the inhibitory
signaling mechanisms that counteract the inflammatory process.A number of caveats need to be mentioned in the interpretation of these results. The
data presented were based on in vitro models of inflammation using MSU, and
we need to see how this works in vivo before coming to any conclusions, as
we have had examples where the in vivo results did not recapitulate the
in vitro findings. They convincingly showed that reducing MICL
expression on the surface of neutrophils enhanced the proinflammatory signature, but
they did not show the converse – that enhanced MICL signaling can further
downmodulate inflammation. Furthermore, the ligands that bind and activate MICL are
unknown, so we have no idea what is the signal or how to reinforce or manipulate
this signaling system. The results presented show that MSU had dual effects on
neutrophils – the first is to downregulate MICL expression, and the second is
to activate IL-8 production. How are these two mechanisms linked? If MSU acts mainly
on the cell membrane internalization of MICL, what is the trigger for the IL-8
secretion? Notwithstanding these uncertainties, the finding that MICL modulates
neutrophil activation in gout suggests that there are a number of counter-regulatory
mechanisms in operation during an inflammatory process. Identifying these mechanisms
may help us to understand the nature of gout as well as open up new therapeutic
perspectives. 相似文献
19.
目的:总结痛风临床病理特点。方法:回顾性分析1例痛风患者的生化机制、临床病理特征、刚果红染色、PAS染色特点、鉴别诊断要点,并复习相关文献。结果:患者主要临床表现为间断性多关节肿痛3年,加重伴发热3个月。体格检查发现患者有多发性皮下结节、多关节肿胀压痛。左腕、左肘皮下结节活检,经HE染色后光镜查见大量肉芽肿性病变,有的多核巨细胞内查见被吞噬的异物,有的病灶尚查见呈均质状物(尿酸盐结晶),其周围有较多异物巨细胞及纤维结缔组织包绕呈结节状,在结节的周边纤维血管周围可查见残留分化成熟的淋巴细胞及少数嗜酸性粒细胞。刚果红、PAS染色均为阴性。偏光显微镜下,刚果红未查见绿色强折光晶体,但见多量略呈淡黄色具有强折光性的晶体呈棒状或梭形。结论:痛风在刚果红染色偏光显微镜下观察呈淡黄色梭形或针状结晶,具有强折光性晶体,但这是否是痛风在刚果红染色的特征尚有待于进一步研究。 相似文献
20.
Hye Mi Jin Tae-Jong Kim Jung-Ho Choi Moon-Ju Kim Young-Nan Cho Kwang-Il Nam Seung-Jung Kee Jang Bae Moon Seok-Yong Choi Dong-Jin Park Shin-Seok Lee Yong-Wook Park 《Arthritis research & therapy》2014,16(2):R88