| 1. |
- Godaly, Gabriela, et al.
(författare)
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Role of epithelial interleukin-8 (IL-8) and neutrophil IL-8 receptor A in Escherichia coli-induced transuroepithelial neutrophil migration
- 1997
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Ingår i: Infection and Immunity. - 1098-5522. ; 65:8, s. 3451-3456
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Tidskriftsartikel (refereegranskat)abstract
- Escherichia coli stimulates neutrophil migration across human uroepithelial cell layers. This study investigated the role of the neutrophil chemokine interleukin-8 (IL-8) in this process. E. coli and IL-1alpha stimulated urinary tract epithelial layers to secrete IL-8 and induced transepithelial neutrophil migration. Anti-IL-8 antibody reduced neutrophil migration across epithelial cell layers, indicating a central role for this chemokine in the migration process. Furthermore, addition of recombinant IL-8 to unstimulated cell layers was sufficient to induce migration. The IL-8 dependence of neutrophil migration was maintained after removal of soluble IL-8 by washing of the cell layers. Flow cytometry analysis with fluorescein isothiocyanate-labelled IL-8 confirmed IL-8's ability to bind to the epithelial cell surface. Indirect immunofluorescence with confocal laser scanning microscopy showed that IL-8 associated with the epithelial cell layers. Prior incubation of neutrophils with antibodies to IL-8 receptor A (IL-8RA) reduced neutrophil migration. Anti-IL-8 RB antibody had no effect on neutrophil migration. These results demonstrate that IL-8 plays a key role in E. coli- or IL-1alpha-induced transuroepithelial migration and suggest that epithelial cell-produced IL-8 interacts with IL-8RA on the neutrophil surface.
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| 2. |
- Godaly, Gabriela, et al.
(författare)
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Role of fimbriae-mediated adherence for neutrophil migration across Escherichia coli-infected epithelial cell layers
- 1998
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Ingår i: Molecular Microbiology. - : Wiley. - 1365-2958 .- 0950-382X. ; 30:4, s. 725-735
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Tidskriftsartikel (refereegranskat)abstract
- This study examined the role of P and type 1 fimbriae for neutrophil migration across Escherichia coli-infected uroepithelial cell layers in vitro and for neutrophil recruitment to the urinary tract in vivo. Recombinant E. coli K-12 strains differing in P or type 1 fimbrial expression were used to infect confluent epithelial layers on the underside of transwell inserts. Neutrophils were added to the upper well, and their passage across the epithelial cell layers was quantified. Infection with the P- and type 1-fimbriated recombinant E. coli strains stimulated neutrophil migration to the same extent as a fully virulent clinical E. coli isolate, but the isogenic non-fimbriated vector control strains had no stimulatory effect. The enhancement of neutrophil migration was adhesion dependent; it was inhibited by soluble receptor analogues blocking the binding of P fimbriae to the globoseries of glycosphingolipids or of type 1 fimbriae to mannosylated glycoprotein receptors. P- and type 1-fimbriated E. coli triggered higher interleukin (IL) 8 secretion and expression of functional IL-8 receptors than non-fimbriated controls, and the increase in neutrophil migration across infected cell layers was inhibited by anti-IL-8 antibodies. In a mouse infection model, P- or type 1-fimbriated E. coli stimulated higher chemokine (MIP-2) and neutrophil responses than the non-fimbriated vector controls. The results demonstrated that transformation with the pap or fim DNA sequences is sufficient to convert an E. coli K-12 strain to a host response inducer, and that fimbriation enhances neutrophil recruitment in vitro and in vivo. Epithelial chemokine production provides a molecular link between the fimbriated bacteria that adhere to epithelial cells and tissue inflammation.
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| 3. |
- Haraoka, Masashi, et al.
(författare)
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Neutrophil recruitment and resistance to urinary tract infection
- 1999
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 180:4, s. 1220-1229
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Tidskriftsartikel (refereegranskat)abstract
- This study examined the role of neutrophil leukocytes for the antibacterial defense at mucosal infection sites. Urinary tract infection (UTI) was established by injection into the bladder lumen of Escherichia coli 1177, a fully virulent clinical isolate. Infection of C3H/HeN (lpsn, lpsn) mice recruited neutrophils into the urinary tract, and bacteria were cleared from kidneys and bladders. The neutrophil response was absent in C3H/HeJ (lpsd, lpsd) mice, and bacteria persisted in the tissues. Peripheral neutrophil depletion of C3H/HeN mice was subsequently achieved by pretreatment with the granulocyte-specific antibody RB6-8C5. The E. coli-induced neutrophil recruitment was inhibited, as shown by immunohistochemistry and tissue myeloperoxidase quantitation. As a consequence, bacterial clearance from kidneys and bladders was drastically impaired. Antibody treatment of C3H/HeJ mice had only a marginal effect. The results show that neutrophils are essential for bacterial clearance from the urinary tract and that the neutrophil recruitment deficiency in C3H/HeJ mice explains their susceptibility to gram-negative UTI.
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| 4. |
- Svanborg, Catharina, et al.
(författare)
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Bacterial virulence in urinary tract infection
- 1997
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Ingår i: Infectious Disease Clinics of North America. - 0891-5520. ; 11:3, s. 513-529
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Tidskriftsartikel (refereegranskat)abstract
- Bacteriuria is associated with acute disease conditions of varying severity.48 and 62 Consequently, the definition of bacterial virulence for the urinary tract depends on the end-point chosen. Acute pyelonephritis is characterized by fever, flank pain, and general malaise. Laboratory findings include pyuria (leukocytes in the urine), elevated acute phase reactants in serum (C reactive protein [CRP], erythrocyte sedimentation rate [ESR]), elevated levels of cytokines in serum and urine, and later increased levels of antibacterial IgA antibodies in urine and serum. Cystitis is characterized by dysuria, urgency, frequency of urination, and sometimes suprapubic pain. Acute cystitis should not be accompanied by acute phase reactants or cytokines in the serum, however, there is pyuria, and IL-6 and IL-8 levels in urine may be elevated. Asymptomatic bacteriuria (ABU) is commonly detected at screening because it is not accompanied by any of the symptoms seen for acute pyelonephritis and acute cystitis. The laboratory findings vary. The patients may have low level cytokine responses and leukocytes in urine, or they may have no host response to infection.
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| 5. |
- Svanborg, Catharina, et al.
(författare)
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Cytokine responses during mucosal infections: role in disease pathogenesis and host defence
- 1999
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Ingår i: Current Opinion in Microbiology. - 1879-0364. ; 2:1, s. 99-103
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Tidskriftsartikel (refereegranskat)abstract
- Mucosal pathogens use diverse and highly specific molecular mechanisms to activate mucosal inflammation. It may even be argued that their virulence depends on the inflammatory response that they induce. Some bacteria target epithelial cells and trigger them to produce inflammatory mediators but others cross the mucosa and activate macrophages or dendritic cells. Although systemic release of inflammatory mediators causes many symptoms and signs of infection, local chemokine production leads to the recruitment of inflammatory cells and lymphocytes that participate directly in the clearance of bacteria from mucosal sites. In this way, mucosal inflammation is a two-edged sword responsible for disease associated tissue destruction and crucial for the antimicrobial defence. Understanding of these pathways should create tools to enhance the defence and interfere with disease.
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