| 1. |
- Nilsdotter-Augustinsson, Åsa, 1962-, et al.
(författare)
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Staphylococcus aureus, but not Staphylococcus epidermidis, modulates the oxidative response and induces apoptosis in human neutrophils
- 2004
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 112:2, s. 109-118
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Tidskriftsartikel (refereegranskat)abstract
- S. epidermidis is the most common isolate in foreign body infections. The aim of this study was to understand why S. epidermidis causes silent biomaterial infections. In view of the divergent inflammatory responses S. epidermidis and S. aureus cause in patients, we analyzed how they differ when interacting with human neutrophils. Neutrophils interacting with S. epidermidis strains isolated either from granulation tissue covering infected hip prostheses or from normal skin flora were tested by measuring the oxidative response as chemiluminescence and apoptosis as annexin V binding. Different S. aureus strains were tested in parallel. All S. epidermidis tested were unable to modulate the oxidative reaction in response to formyl-methionyl-leucyl-phenylalanine (fMLP) and did not provoke, but rather inhibited, apoptosis. In contrast, some S. aureus strains enhanced the oxidative reaction, and this priming capacity was linked to p38-mitogen-activated-protein-kinase (p38-MAPK) activation and induction of apoptosis. Our results may explain why S. epidermidis is a weak inducer of inflammation compared to S. aureus, and therefore responsible for the indolent and chronic course of S. epidermidis biomaterial infections.
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| 2. |
- Wilsson, Åsa, 1966-
(författare)
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On the interaction between human neutrophils and Staphylococcus aureus
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Intracellular free calcium is a key second messenger and has been shown to regulate several crucial functions in human neutrophils. The results show that a rise in [Ca2+], is an absolute requirement for efficient killing of serum-opsonized Staphylococcus aureus by human neutrophils. The reduced killing in the absence of Ca2+ was not due to an inhibited ingestion of the S. aureus bacteria but to impairment of the subsequent production of oxygen radicals.S. aureus is a bacterium which binds to extracellular matrix proteins such as vitronectin. When studying the role of Ca2+ during phagocytosis of S. aureus adherent to vitronectin-coated surfaces, the results show that a rise in [Ca2+], is not a prerequisite for ingestion per se. However, Ca2+ control neutrophil migration on vitronectin, by regulating reversible integrindependent adhesion of the neutrophils.The intracellular signalling events of the neutrophils induced by S. aureus were also evaluated. The results demonstrate that S. aureus induces both priming and apoptosis in the neutrophils. This was restricted to viable and not heat-killed bacteria. During priming tyrosine phosphorylation of PLCγ2 and Syk is increased. In addition, the Src-family protein kinase Lyn is activated as well by these bacteria. Inhibition of these proteins by selective drugs abrogates priming of the neutrophils, indicating that these proteins participate in neutrophil priming. Interaction of neutrophils with S. aureus as well as a S. aureus-derived factor induces apoptosis in the neutrophils, and this is regulated by p38 MAPK.Taken together, this investigation shows that the Ca2+-dependent processing of bacteria by human neutrophils leads to several cellular responses affecting inflammation, such as oxidative activation, tyrosine phosphorylation, priming and apoptosis.
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| 3. |
- Lundqvist-Gustafsson, Helen, 1966-, et al.
(författare)
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Involvement of p38-mitogen-activated protein kinase in staphylococcus aureus-induced neutrophil apoptosis
- 2001
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Ingår i: Journal of Leukocyte Biology. - 0741-5400 .- 1938-3673. ; 70:4, s. 642-648
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Tidskriftsartikel (refereegranskat)abstract
- Apoptosis occurred in human neutrophils within an hour of exposure to viable serumopsonized Staphylococcus aureus, as indicated by appearance of cells with condensed nuclei, fragmented DNA, and increased phosphatidylserine exposure. In contrast, serum-opsomized, heat-killed S. aureus did not induce apoptosis. This discrepancy could not be explained by differences in bacterial uptake or total NADPH-oxidase activity. Suppressing phagocytosis by pretreating the neutrophils with cytochalasin b or by using nonopsonized bacteria did not prevent apoptosis. A supernatant from bacteria grown for 2 h in nutrient broth had a strong proapoptotic influence that was abrogated by heat treatment. Exposure to viable S. aureus or supernatant also led to activation of p38-mitogen-activated protein kinase in the neutrophils. Inhibition of this kinase with SB203580 reduced the apoptosis-inducing capacity of both bacteria and supernatant. We conclude that S. aureus activates p38-mitogen-activated protein kinase in neutrophils and induces apoptosis, probably mediated by a bacteria-derived soluble factor(s).
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| 4. |
- Löfgren, Ragnhild, et al.
(författare)
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CR3, FcγRIIA and FcγRIIIB induce activation of the respiratory burst in human neutrophils : the role of intracellular Ca2+, phospholipase D and tyrosine phosphorylation
- 1999
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Ingår i: Biochimica et Biophysica Acta. Molecular Cell Research. - 0167-4889 .- 1879-2596. ; 1452:1, s. 46-59
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Tidskriftsartikel (refereegranskat)abstract
- Human neutrophils express two different types of phagocytic receptors, complement receptors (CR) and Fc receptors. In order to characterize the different signaling properties of each receptor we have used non-adherent human neutrophils and investigated CR3, FcγRIIA and FcγRIIIB for their signaling capacity. Selective activation of each receptor was achieved by coupling specific antibodies to heat-killed Staphylococcus aureus particles, Pansorbins, through their Fc moiety. Despite the fact that these particles are not phagocytosed, we show that addition of Pansorbins with anti-CD18 antibodies recognizing CR3 induced prominent signals leading to a respiratory burst. Stimulation with anti-FcγRIIIB Pansorbins induced about half of the response induced by anti-CR3 Pansorbins, whereas anti-FcγRIIA Pansorbins induced an even weaker signal. However, FcγRIIA induced strong phosphorylation of p72syk whereas FcγRIIIB induced only a very weak p72syk phosphorylation. During CR3 stimulation no tyrosine phosphorylation of p72syk was seen. Both phospholipase D and NADPH oxidase activities were dependent on intracellular calcium. This is in contrast to tyrosine phosphorylation of p72syk that occurred even in calcium-depleted cells, indicating that oxygen metabolism does not affect p72syk phosphorylation. Inhibitors of tyrosine phosphorylation blocked the respiratory burst induced by both FcγRIIA and FcγRIIIB as well as CR3. This shows that tyrosine phosphorylation of p72syk is an early signal in the cascade induced by FcγRIIA but not by CR3.
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