Platelets may inhibit leucotriene biosynthesis by human neutrophils at the integrin level

Chabannes, B.; Molière, Patrick; Merhi-Soussi, Faten; Poubelle, Patrice E.; Lagarde, Michel

doi:10.1046/j.1365-2141.2003.04271.x

Cited by 8 publications

(8 citation statements)

References 42 publications

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“…In that respect, integrin activation by fibronectin induced IL-8 and GRO expressions in melanoma cells and monocytes (32,33). In addition, integrins modulate leukotriene production and secretion by neutrophils (34). Because SPARC regulates fibronectin levels in endothelial cells (35) and modulates integrin-mediated melanoma cell adhesion to different matrices, 6 we hypothesize that SPARC might act on an integrin-dependent pathway to regulate IL-8, GRO, and leukotriene production.…”

Section: Resultsmentioning

confidence: 99%

Secreted Protein Acidic and Rich in Cysteine Produced by Human Melanoma Cells Modulates Polymorphonuclear Leukocyte Recruitment and Antitumor Cytotoxic Capacity

et al. 2005

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The expression of secreted protein acidic and rich in cysteine (SPARC) has been associated with the malignant progression of different types of human cancer. SPARC was associated with tumor cell capacity to migrate and invade, although its precise role in tumor progression is still elusive. In the present study, we show that SPARC produced by melanoma cells modulates the antitumor activity of polymorphonuclear leukocytes (PMN). Administration to nude mice of human melanoma cells in which SPARC expression was transiently or stably knocked down by antisense RNA (SPARC-sup cells) promoted PMN recruitment and obliterated tumor growth even when SPARC-sup cells accounted for only 10% of injected malignant cells. In addition, SPARC-sup cells stimulated the in vitro migration and triggered the antimelanoma cytotoxic capacity of human PMN, an effect that was reverted in the presence of SPARC purified from melanoma cells or by reexpressing SPARC in SPARC-sup cells. Leukotrienes, interleukin 8, and growth-related oncogene, in combination with Fas ligand and interleukin 1, mediated SPARC effects. These data indicate that SPARC plays an essential role in tumor evasion from immune surveillance through the inhibition of the antitumor PMN activity. (Cancer Res 2005; 65(12): 5123-32)

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Section: Resultsmentioning

confidence: 99%

Secreted Protein Acidic and Rich in Cysteine Produced by Human Melanoma Cells Modulates Polymorphonuclear Leukocyte Recruitment and Antitumor Cytotoxic Capacity

et al. 2005

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“…Furthermore, activation of the IgE receptor on platelets (FcεR1) results in the release of serotonin and the cytokine, Regulated on Activation, Normal T-cell Expressed and Secreted, or RANTES, which is important in allergic inflammation (36). Platelets have also been shown to strongly inhibit arachodonic acid 5-lipoxygenation in neutrophils through the fibrinogen receptor (11), and the leukotrienes created by this mechanism are one of the major drug targets in asthma. Together, these previous results and those presented in this study suggest that platelet function, possibly influenced by ITGB3 genotype, may play a direct role in asthma and atopy.…”

Section: Discussionmentioning

confidence: 99%

“…ITGB3 encodes a ␤-integrin that comprises part of the platelet-and monocyte-specific heterodimeric receptor for fibrinogen and the widely expressed receptor for vitronectin. Fibrinogen receptors regulate platelet aggregation, hemostasis, and thrombosis, and they interact with P-selectin to mediate the adhesion of platelets to neutrophils (11). Vitronectin receptors have roles in leukocyte adhesion and extravasation (12), are important in neutrophil braking during transit through the extracellular matrix (13), and signal mast cell degranulation (14).…”

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confidence: 99%

Variation in ITGB3 Is Associated with Asthma and Sensitization to Mold Allergen in Four Populations

Weiss

Lester

Gern

et al. 2005

Am J Respir Crit Care Med

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Rationale: Recent genetic studies have implicated integrins in asthma and atopy susceptibility. We therefore evaluated the integrin-␤3 gene (ITGB3), an integrin gene within an asthma linkage peak on chromosome 17, as a candidate for susceptibility to asthma-and atopy-related phenotypes. Methods and Measurements: We genotyped and performed association tests on 19 single nucleotide polymorphisms in ITGB3 in the Hutterites, a founder population, and in three outbred replication populations. Main Results: Variation in ITGB3 was strongly associated with susceptibility to bronchial hyperresponsiveness and protection from allergic sensitization to mold allergens in this population. Three independent case-control populations representing Caucasians and African Americans were used to replicate this finding, also revealing ITGB3 alleles that are associated with asthma susceptibility and protection from mold allergen sensitization. Conclusions: This study provides evidence that ITGB3 plays a role in the pathogenesis of asthma and sensitization to mold allergens.

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“…We speculate that platelets might present their CS to PMNL, and inhibition of LT synthesis may be a consequence of such a lipid exchange. Physiological concentrations of platelets inhibited LT biosynthesis in human neutrophils in an adhesion‐dependent manner [49,50]. After degranulation by thrombin under nonaggregating conditions, platelets lost their inhibitory activity [50].…”

Section: Discussionmentioning

confidence: 99%

Cholesterol and its anionic derivatives inhibit 5‐lipoxygenase activation in polymorphonuclear leukocytes and MonoMac6 cells

et al. 2006

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Mammalian 5-lipoxygenase (5-LO) converts arachidonic acid (AA) to 5-hydroperoxyeicosatetraenoic acid (5-HPETE) and further to leukotriene A4 (LTA4) [1]. This substance is a key intermediate in the biosynthesis of two leukotriene families that act as potent mediators of cell proliferation [2], apoptosis [3], tumorigenesis and inflammatory processes such as allergy, atherosclerosis and asthma [4,5]. 5-LO is activated by intracellular Ca 2+ influx that leads to translocation and binding of 5-LO to the nuclear membrane [6][7][8][9][10][11]. It is commonly observed that the N-terminal domain of the enzyme may function like the protein kinase C C2 domain and facilitates Ca 2+ -mediated membrane binding [12][13][14][15][16].There are two main physicochemical factors influencing translocation of 5-LO to the membrane. First, the calcium-ion binding counteracts electrostatic repulsion of anionic C2 domain of 5-LO at the surface of anionic membranes [15]. Secondly, it may be regulated by membrane surface charge and membrane lipids. It was shown that phosphatidyl choline (PC) head groups facilitate the 5-LO C2-like domain binding to membranes, and that Trp13, Trp75, Trp102 of 5-LO are involved in these protein-lipid interactions [15] 5-Lipoxygenase (5-LO) is the key enzyme in the biosynthesis of leukotrienes (LTs), biological mediators of host defense reactions and of inflammatory diseases. While the role of membrane binding in the regulation of 5-LO activity is well established, the effects of lipids on cellular activity when added to the medium has not been characterized. Here, we show such a novel function of the most abundant sulfated sterol in human blood, cholesterol sulfate (CS), to suppress LT production in human polymorphonuclear leukocytes (PMNL) and Mono Mac6 cells. We synthesized another anionic lipid, cholesterol phosphate, which demonstrated a similar capacity in suppression of LT synthesis in PMNL. Cholesteryl acetate was without effect. Cholesterol increased the effect of CS on 5-LO product synthesis. CS and cholesterol also inhibited arachidonic acid (AA) release from PMNL. Addition of exogenous AA increased the threshold concentration of CS required to inhibit LT synthesis. The effect of cholesterol and its anionic derivatives can arise from remodeling of the cell membrane, which interferes with 5-LO activation. The fact that cellular LT production is regulated by sulfated cholesterol highlights a possible regulatory role of sulfotransferases ⁄ sulfatases in 5-LO product synthesis.

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Platelets may inhibit leucotriene biosynthesis by human neutrophils at the integrin level

Cited by 8 publications

References 42 publications

Secreted Protein Acidic and Rich in Cysteine Produced by Human Melanoma Cells Modulates Polymorphonuclear Leukocyte Recruitment and Antitumor Cytotoxic Capacity

Secreted Protein Acidic and Rich in Cysteine Produced by Human Melanoma Cells Modulates Polymorphonuclear Leukocyte Recruitment and Antitumor Cytotoxic Capacity

Variation in ITGB3 Is Associated with Asthma and Sensitization to Mold Allergen in Four Populations

Cholesterol and its anionic derivatives inhibit 5‐lipoxygenase activation in polymorphonuclear leukocytes and MonoMac6 cells

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