| 1. |
- Malipiero, Ursula, et al.
(författare)
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TGF beta receptor II gene deletion in leucocytes prevents cerebral vasculitis in bacterial meningitis
- 2006
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Ingår i: Brain. - : Oxford University Press (OUP). - 1460-2156 .- 0006-8950. ; 129, s. 2404-2415
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Tidskriftsartikel (refereegranskat)abstract
- In bacterial meningitis, chemokines lead to recruitment of polymorphonuclear leucocytes (PMN) into the CNS. At the site of infection in the subarachnoid space, PMN release reactive oxygen species, reactive nitrogen intermediates (RNI) and interleukin-1 beta (IL-1 beta). Although these immune factors assist in clearance of bacteria, they also result in neuronal injury associated with meningitis. Transforming growth factor beta (TGF beta) is a potent deactivator of PMN and macrophages since TGF beta suppresses the production of ROI, RNI and IL-1. Here, we report that the deletion of the TGF beta receptor II gene in PMN enhances PMN recruitment into the CNS of mice with Streptococcus pneumoniae meningitis. This was associated with more efficient clearance of bacteria, and almost complete prevention of intracerebral necrotizing vasculitis. Differences in PMN in the CNS of infected control mice and mice lacking TGF beta receptor II were not explained by altered expression of chemokines acting on PMN. Instead, TGF beta was found to impair the expression of L (leucocyte)-selectin on PMN from control mice but not from mice lacking TGF beta receptor II. L-Selectin is known to be essential for PMN recruitment in bacterial meningitis. We conclude that defective TGF beta signalling in PMN is beneficial in bacterial meningitis by ameliorating migration of PMN and bacterial clearance.
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| 2. |
- Pruenster, Monika, et al.
(författare)
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Extracellular MRP8/14 is a regulator of β2 integrin-dependent neutrophil slow rolling and adhesion.
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Myeloid-related proteins (MRPs) 8 and 14 are cytosolic proteins secreted from myeloid cells as proinflammatory mediators. Currently, the functional role of circulating extracellular MRP8/14 is unclear. Our present study identifies extracellular MRP8/14 as an autocrine player in the leukocyte adhesion cascade. We show that E-selectin-PSGL-1 interaction during neutrophil rolling triggers Mrp8/14 secretion. Released MRP8/14 in turn activates a TLR4-mediated, Rap1-GTPase-dependent pathway of rapid β2 integrin activation in neutrophils. This extracellular activation loop reduces leukocyte rolling velocity and stimulates adhesion. Thus, we identify Mrp8/14 and TLR4 as important modulators of the leukocyte recruitment cascade during inflammation in vivo.
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| 3. |
- Wache, Christina, et al.
(författare)
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Myeloid-related protein 14 promote inflammation and injury in meningitis.
- 2015
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 212:2, s. 247-257
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Tidskriftsartikel (refereegranskat)abstract
- Neutrophilic inflammation often persists over days despite efficient antibiotic treatment and contributes to brain damage in bacterial meningitis. We proposed here that MRP14, an abundant cytosolic protein in myeloid cells, acts as an endogenous danger signal, driving inflammation and aggravating tissue injury.
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