| 1. |
- Betten, Åsa, 1967, et al.
(författare)
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Oxygen radical-induced natural killer cell dysfunction: role of myeloperoxidase and regulation by serotonin
- 2004
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Ingår i: J Leukoc Biol. ; 75:6, s. 1111-5
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Tidskriftsartikel (refereegranskat)abstract
- Natural killer (NK) cells are functionally suppressed and induced to apoptosis by reactive oxygen species (ROS) produced by mononuclear phagocytes (MPs). These inhibitory events are reversed by the biogenic amine serotonin. MPs generate hydrogen peroxide (H(2)O(2)), which is processed further by myeloperoxidase (MPO) to even more toxic compounds. Earlier studies suggest that serotonin scavenges MP-derived oxygen radicals generated by the MPO-H(2)O(2) system. These findings led us to explore the capability of MPO-deficient MPs to induce NK cell dysfunction. We show that MPs recovered from subjects with MPO deficiency trigger inhibition of NK cells. In addition, MPs recovered from healthy subjects conveyed suppression of NK cells in the presence of the MPO inhibitor ceruloplasmin. We conclude that ROS-dependent inhibition of NK cell function is unrestricted by the availability of MPO-derived oxygen radicals and that the protecting properties of serotonin may operate in the absence of functional MPO. Our data suggest a complex mechanism of MP-induced NK cell inhibition, which comprises the generation of interchangeable oxygen radicals.
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| 2. |
- Bylund, Johan, 1975, et al.
(författare)
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Cytochalasin B triggers a novel pertussis toxin sensitive pathway in TNF-alpha primed neutrophils
- 2004
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Ingår i: BMC cell biology. - 1471-2121. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cytochalasin B does not directly activate the oxygen-radical-producing NADPH oxidase activity of neutrophils but transfers desensitized G-protein coupled receptors (GPCR) into an active signaling state by uncoupling GCPR from the cytoskeleton. The receptor uncoupling results in respiratory burst activity when signals generated by reactivated formyl peptide receptors trigger the NADPH-oxidase to produce superoxide anions. RESULTS: Tumor necrosis factor alpha (TNF-alpha) primes neutrophils for subsequent activation by cytochalasin B. Pretreatment with TNF-alpha induced mobilization of receptor-storing neutrophil organelles, suggesting that receptor up-regulation significantly contributes to the response, but the receptor mobilization was not sufficient for induction of the cytochalasin B sensitive state. The TNF-alpha primed state resembled that of the desensitized non-signaling state of agonist-occupied neutrophil formyl peptide receptors. The fact that the TNF-alpha primed, cytochalasin B-triggered activation process was pertussis toxin sensitive suggests that the activation process involves a GPCR. Based on desensitization experiments the unidentified receptor was found to be distinct from the C5a receptor as well as the formyl peptide receptor family members FPR and FPRL1. Based on the fact the occupied and desensitized receptors for interleukin-8 and platelet activating factor could not be reactivated by cytochalasin B, also these could be excluded as receptor candidates involved in the TNF-alpha primed state. CONCLUSIONS: The TNF-alpha-induced priming signals could possibly trigger a release of an endogenous GPCR-agonist, amplifying the response to the receptor-uncoupling effect of cytochalasin B. However, no such substance could be found, suggesting that TNF-alpha can transfer G-protein coupled receptors to a signaling state independently of agonist binding.
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| 3. |
- Hellstrand, Kristoffer, 1956, et al.
(författare)
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Alleviating oxidative stress in cancer immunotherapy: a role for histamine?
- 2000
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Ingår i: Medical oncology (Northwood, London, England). - 1357-0560. ; 17:4, s. 258-69
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin-2 is a remarkable activator of lymphocytes with anti-neoplastic properties such as T-cells or natural killer cells, but tumor regression only rarely occurs in interleukin-2-treated cancer patients. In this review, we focus on interactions between monocytes/macrophages and T-cells/natural killer-cells, and in particular the role of such interactions for the outcome of cancer immunotherapy with interleukin-2. We propose that interleukin-2 therapy should be supplemented with compounds that alleviate toxicity inflicted by monocyte/macrophage-derived reactive oxygen metabolites within and around tumors. The hypothesis is founded on data demonstrating that (i) functions of intratumoral lymphocytes in many human malignant tumors are inhibited by reactive oxygen metabolites, generated by neighboring monocytes/macrophages, (ii) interleukin-2 only weakly activates T-cells or natural killer cells in an environment of oxidative stress, and (iii) inhibitors of the formation of reactive oxygen metabolites or scavengers of reactive oxygen metabolites synergize with interleukin-2 to activate these lymphocyte subsets. We also review the preclinical background to the use of histamine dihydrochloride, an inhibitor of reactive oxygen metabolite formation in monocytes/macrophages, as a supplement to cancer immunotherapy with interleukin-2.
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| 4. |
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| 5. |
- Mellqvist, Claes
(författare)
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Proterozoic crustal growth along the Archaean continental margin in the Luleå and Jokkmokk areas, northern Sweden
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Den Arkeisk-Proterozoiska plattgränsen i norra Sverige har undersökts med hjälp utav fältarbete med både berggrundskartering och provtagning för geokemisk och isotopgeokemisk analys. Gränsen har studerats i både Luleå och Jokkmokkområdena för att man där skall kunna dra gränsen mer i detalj. Sm-Nd isotoper har används som ett verktyg för att se om de provtagna bergarterna innehåller spår utav den äldre (Arkeiska) eller är är bildade i en yngre (Proterozoisk) miljö. Det har visat sig att övergången är relativt skarp i Luleåområdet men gradiell i Jokkmokkområdet. En arbetsmodell har varit att det yngre materialet i söder har kolliderat med den äldre kontinenten under den sk Svekofenniska orogenesen. Detta resulterade i att de södra delarna sköts upp ovanpå det äldre. Prov tagna av bergarter som är bildade både före och efter denna kollision har visat att modellen inte förändrats snarare styrkts. För att förklara de processer som var verksamma under tiden som bergarterna bildades så har en del detaljstudier bedrivits i huvudsak i trakterna kring Luleå. Arbetet presenteras i sju stycken artiklar som behandlar både små och storskalig problematik.
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| 8. |
- Mellqvist, Claes, et al.
(författare)
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Some aspects on the subdivision of the Haparanda and Jörn intrusive suites in northern Sweden
- 2003
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Ingår i: GFF. - : Informa UK Limited. - 1103-5897 .- 2000-0863. ; 125:2, s. 77-85
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Tidskriftsartikel (refereegranskat)abstract
- The geographical subdivision between the Haparanda and the Jörn suites of intrusive rocks in northern Sweden has not been very well defined. Early stratigraphical schemes placed these two granitoid suites in two separate orogenic cycles, where the Jörn belonged to the older cycle and Haparanda to the younger. Our present knowledge regarding the isotopic ages of these rocks in northern Sweden has changed this view, but has also made the distinction between the two suites less clear. Based on recent Sm–Nd isotopic work combined with geochemistry and some new U–Pb zircon data, we point out some similarities as well as some differences between the Jörn and Haparanda suites of rocks. Two U–Pb zircon age determinations performed give upper intercept ages of 1891±32 Ma and 1861±19 Ma which are interpreted as maximum ages. The two samples are taken from the Luleå area, on each side of the Archaean–Proterozoic boundary, as defined by Sm–Nd isotopic analyses of c.1.9 Ga old intrusive rocks combined with the southern limit of outcropping Archaean rocks. On the basis of new results together with results from previous studies of areas north and south of the Archaean–Proterozoic boundary, we also suggest how to separate the Haparanda and Jörn suites of rocks due to their geochemical, and isotope geochemical, characteristics. The Haparanda suite generally has negative εNd(t) values and was formed within or in marginal parts of the Archaean craton. The Jörn suite was formed in an juvenile, island-arc terrane, that was accreted to the Archaean craton during the later, collisional stages of the Svecokarelian orogeny. In a similar way, we connect the Haparanda suite of rocks with the Archaean craton, and the Jörn suite of rocks with Svecofennian juvenile crust.
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| 11. |
- Pellmé, Sara, 1975, et al.
(författare)
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Localization of human neutrophil interleukin-8 (CXCL-8) to organelle(s) distinct from the classical granules and secretory vesicles
- 2006
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Ingår i: J Leukoc Biol. - : Oxford University Press (OUP). ; 79, s. 564-573
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Tidskriftsartikel (refereegranskat)abstract
- Mature human neutrophils contain small amounts of interleukin-8 [CXC chemokine ligand 8 (CXCL-8)], which upon proinflammatory activation, increases significantly. It has been suggested that the CXCL-8 content of resting human neutrophils is stored in the secretory vesicles. Here, we have used a fractionation technique, which allows isolation of these vesicles, and we find that CXCL-8 neither colocalizes with the secretory vesicles nor with markers of any of the classical neutrophil granules. To increase resolution in the system, we induced CXCL-8 production by lipopolysaccharide. After 8 h of stimulation, CXCL-8 was visualized within the cell using immunoelectron microscopy. The images revealed CXCL-8-containing stuctures resembling neutrophil granules, and these were distinct from all known neutrophil organelles, as shown by double immunostaining. Further, the CXCL-8 organelle was present in nonstimulated neutrophil cytoplasts, entities lacking all other known granules and secretory vesicles. Upon fractionation of the cytoplasts, CXCL-8 was found to partly cofractionate with calnexin, a marker for endoplasmic reticulum (ER). Thus, part of CXCL-8 may be localized to the ER or ER-like structures in the neutrophil.
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