| 1. |
- Johansson, Joakim, et al.
(författare)
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Dynamics of leucocytes correlate with increased pulmonary vascular permeability and decreased PaO2:FiO2 ratio early after major burns
- 2009
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: The lung is affected soon after a major burn as indicated by a decreased PaO2:FiO2 ratio. The exact mechanism underlying this is not known. Polymorphonuclear leucocytes (PMN) are activated systemically and their numbers are largely increased soon after a burn followed by a rapid decline to low normal or subnormal numbers within 24 hours, possibly by increased extravasation. Experimental data have supported the hypothesis that an important target for this extravasation is the lungs. Other studies also show that when PMN adhere to endothelial cells they increase vascular permeability, and this effect is mediated, at least in part, by release of heparin binding protein (HBP, also known as CAP-37 and azurocidin). We hypothesised that there is a relation between early increased pulmonary vascular permeability or a decreased PaO2:FiO2 ratio and the dynamic change in blood leucocytes after a burn, possibly mediated by the local release of HBP.Material and methods: This is a prospective, descriptive, exploratory, singlecentre study at a national burn centre. We investigated the dynamic changes of leucocytes in blood, plasma concentrations of HBP, pulmonary vascular permeability index (PVPI) by thermodilution, and PaO2:FiO2 ratios in 20 patients during the first 21 days after a major burn (20% >total burn surface area %).Results: Median total burn surface area was 40% (IQR 25-52) and full thickness burn 28% (IQR 2-39). There was a correlation between the early (<24 hours) alteration in circulating white blood cell count and both early increased vascular permeability in the lung (r=0.63, p=0.004) and the decreased oxygenation index defined as PaO2:FiO2 < 27 kPa (p=0.004). There were no associations between plasma concentrations of HBP and measured pulmonary vascular permeability or PaO2:FiO2 ratios.Conclusions: The results indicate that trapping of leucocytes in the lung may be an important factor in early increased pulmonary vascular permeability and decrease of the PaO2:FiO2 ratio. Our data do not support the idea that HBP, assessed by systemic plasma concentrations, mediate this effect.
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| 2. |
- Johansson, Joakim, et al.
(författare)
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Neutrophil-derived heparin binding protein-A mediator of increased vascular permeability after burns?
- 2009
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Ingår i: BURNS. - : Elsevier BV. - 0305-4179 .- 1879-1409. ; 35:8, s. 1185-1187
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Tidskriftsartikel (refereegranskat)abstract
- Increased vascular permeability and oedema formation constitute a major clinical challenge following burns. Several clinical studies show that leukocytes are systemically activated following burns. Neutrophils have the capability to increase vascular permeability via mechanisms thought to involve the release of heparin binding protein (HBP). We hypothesised that HBP is elevated in plasma after major burns due to a systemic inflammatory response and investigated plasma-HBP concentrations in 10 severely burned patients daily for 1 week following the burn. Five-fold higher levels in plasma-HBP concentration compared to a control group were detected on the first day after injury, followed by a steep reduction in the time-period that corresponds to the last part of the hyperpermeability phase. These data are in accordance with the hypothesis that HBP may function as a mediator of the early bum-induced increase in vascular permeability, and call for further studies to confirm a possible cause-and-effect relationship between HBP and oedema formation following burns.
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| 3. |
- Karlsson, Hanna L, et al.
(författare)
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Comparison of genotoxic and inflammatory effects of particles generated by wood combustion, a road simulator and collected from street and subway
- 2006
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Ingår i: Toxicology Letters. - : Elsevier BV. - 0378-4274 .- 1879-3169. ; 165:3, s. 203-211
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Tidskriftsartikel (refereegranskat)abstract
- The health effects of exposure to airborne particles are of increasing concern in society. In order to protect public health, a clarification of the toxic properties of particles from different sources is of importance. The aim of this study was to investigate and compare the genotoxicity and the ability to induce inflammatory mediators of nine different particle types from wood and pellets combustion, from tire–road wear and collected from an urban street and a subway station. The comet assay was used to assess genotoxicity after exposure of the human lung cell line A549. Inflammatory effects were measured as induction of IL-6, IL-8 and TNF-α after exposure of human macrophages. We found that all particles tested caused DNA damage and those from the subway caused more damage than the other particles (p < 0.001) likely due to redox-active iron. In contrast, particles collected from an urban street were most potent to induce inflammatory cytokines. Particles from tire–road wear collected using a road simulator were genotoxic and able to induce cytokines. Finally, more effective combustion of wood led to less emission of particles, but those emitted did not show less toxicity in this study.
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| 4. |
- Soehnlein, Oliver, et al.
(författare)
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Neutrophil primary granule proteins HBP and HNP1-3 boost bacterial phagocytosis by human and murine macrophages.
- 2008
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Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 118:10, s. 3491-3502
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Tidskriftsartikel (refereegranskat)abstract
- In acute inflammation, infiltrating polymorphonuclear leukocytes (also known as PMNs) release preformed granule proteins having multitudinous effects on the surrounding environment. Here we present what we believe to be a novel role for PMN-derived proteins in bacterial phagocytosis by both human and murine macrophages. Exposure of macrophages to PMN secretion markedly enhanced phagocytosis of IgG-opsonized Staphylococcus aureus both in vitro and in murine models in vivo. PMN secretion activated macrophages, resulting in upregulation of the Fcgamma receptors CD32 and CD64, which then mediated the enhanced phagocytosis of IgG-opsonized bacteria. The phagocytosis-stimulating activity within the PMN secretion was found to be due to proteins released from PMN primary granules; thorough investigation revealed heparin-binding protein (HBP) and human neutrophil peptides 1-3 (HNP1-3) as the mediators of the macrophage response to PMN secretion. The use of blocking antibodies and knockout mice revealed that HBP acts via beta(2) integrins, but the receptor for HNP1-3 remained unclear. Mechanistically, HBP and HNP1-3 triggered macrophage release of TNF-alpha and IFN-gamma, which acted in an autocrine loop to enhance expression of CD32 and CD64 and thereby enhance phagocytosis. Thus, we attribute what may be a novel role for PMN granule proteins in regulating the immune response to bacterial infections.
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| 5. |
- Soehnlein, Oliver, et al.
(författare)
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Neutrophil secretion products pave the way for inflammatory monocytes
- 2008
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 112:4, s. 1461-1471
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Tidskriftsartikel (refereegranskat)abstract
- The leukocyte response in inflammation is characterized by an initial recruitment of polymorphonuclear leukocytes (PMN) preceding a second wave of monocytes to the site of injury or infection. In the mouse, 2 populations of monocytes have been identified, Gr1-CCR2-CX3CR1(hi) resident monocytes and Gr1+CCR2+CX3CR1(lo) inflammatory monocytes. Here, intravital microscopy of the musculus cremasterand a subcutaneous air pouch model were used to investigate a possible link between PMN extravasation and the subsequent emigration of inflammatory monocytes in response to local stimulation with PAR In mice that were made neutropenic by injection of a PMN-depleting antibody, the extravasation of inflammatory monocytes, but not resident monocytes, was markedly reduced compared with mice with intact white blood cell count but was restored by local treatment with secretion of activated PMN. Components of the PMN secretion were found to and further examination revealed PMN-derived LL-37 and heparin-binding protein (HBP/CAP37/azurocidin) as primary mediators of the recruitment of inflammatory monocytes via activation of formyl-peptide receptors. These data show that LL-37 and HBP specifically stimulate mobilization of inflammatory monocytes. This cellular cross-talk functionally results in enhanced cytokine levels and increased bacterial clearance, thus boosting the early immune response.
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