Limits...
Interleukin 8 receptor deficiency confers susceptibility to acute experimental pyelonephritis and may have a human counterpart.

Frendéus B, Godaly G, Hang L, Karpman D, Lundstedt AC, Svanborg C - J. Exp. Med. (2000)

Bottom Line: Neutrophils migrate to infected mucosal sites that they protect against invading pathogens.The experimental UTI model demonstrated that IL-8R-dependent mechanisms control the urinary tract defense, and that neutrophils are essential host effector cells.The results provide a first molecular clue to disease susceptibility of patients prone to acute pyelonephritis.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Immunology, and Glycobiology, Institute of Laboratory Medicine, Lund University, S-223 62 Lund, Sweden.

ABSTRACT
Neutrophils migrate to infected mucosal sites that they protect against invading pathogens. Their interaction with the epithelial barrier is controlled by CXC chemokines and by their receptors. This study examined the change in susceptibility to urinary tract infection (UTI) after deletion of the murine interleukin 8 receptor homologue (mIL-8Rh). Experimental UTIs in control mice stimulated an epithelial chemokine response and increased chemokine receptor expression. Neutrophils migrated through the tissues to the epithelial barrier that they crossed into the lumen, and the mice developed pyuria. In mIL-8Rh knockout (KO) mice, the chemokine response was intact, but the epithelial cells failed to express IL-8R, and neutrophils accumulated in the tissues. The KO mice were unable to clear bacteria from kidneys and bladders and developed bacteremia and symptoms of systemic disease, but control mice were fully resistant to infection. The experimental UTI model demonstrated that IL-8R-dependent mechanisms control the urinary tract defense, and that neutrophils are essential host effector cells. Patients prone to acute pyelonephritis also showed low CXC chemokine receptor 1 expression compared with age-matched controls, suggesting that chemokine receptor expression may also influence the susceptibility to UTIs in humans. The results provide a first molecular clue to disease susceptibility of patients prone to acute pyelonephritis.

Show MeSH

Related in: MedlinePlus

Defective CXCR1 surface expression on neutrophils from children with acute pyelonephritis. (a) CXCR1 receptor expression, quantified by flow cytometry, was reduced in patient 1 (open peak) compared with control 1 (filled peak; for fluorescence intensity see Table ). CXCR2 receptor expression did not differ between the patient and control samples. The dotted line shows the background fluorescence of the IgG control Ab. (b) Confocal images illustrating the difference in neutrophil CXCR1 expression between neutrophils from patient 1 (top left) and control 1 (top right). There was no difference in CXCR2 expression between the patient and the control cells (bottom panels). (c) Decreased CXCR1 mRNA in neutrophils from children with acute pyelonephritis. CXCR1 mRNA was quantified by the RNA protection assay. Samples from patients (P1, P2–P8) or controls (C1, C2–C8) were loaded in alternate wells. CXCR1 mRNA was reduced in all of the patients compared with the controls. The bottom two lanes show mRNA for the housekeeping genes L32 and GAPDH. Data are summarized in Table .
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2193279&req=5

Figure 6: Defective CXCR1 surface expression on neutrophils from children with acute pyelonephritis. (a) CXCR1 receptor expression, quantified by flow cytometry, was reduced in patient 1 (open peak) compared with control 1 (filled peak; for fluorescence intensity see Table ). CXCR2 receptor expression did not differ between the patient and control samples. The dotted line shows the background fluorescence of the IgG control Ab. (b) Confocal images illustrating the difference in neutrophil CXCR1 expression between neutrophils from patient 1 (top left) and control 1 (top right). There was no difference in CXCR2 expression between the patient and the control cells (bottom panels). (c) Decreased CXCR1 mRNA in neutrophils from children with acute pyelonephritis. CXCR1 mRNA was quantified by the RNA protection assay. Samples from patients (P1, P2–P8) or controls (C1, C2–C8) were loaded in alternate wells. CXCR1 mRNA was reduced in all of the patients compared with the controls. The bottom two lanes show mRNA for the housekeeping genes L32 and GAPDH. Data are summarized in Table .

Mentions: Neutrophil CXCR1 receptor expression was low in children with pyelonephritis compared with the age-matched controls (P < 0.03). This is exemplified in Fig. 6 a for patient 1 and control 1. By confocal microscopy, fewer CXCR1+ cells were observed in the patients than in the controls (Fig. 6 b), and flow cytometry showed reduced CXCR1 fluorescence intensity of the patient neutrophils compared with the controls. Pairwise analysis of CXCR1 expression on neutrophils from 12 patients with recurrent pyelonephritis and 12 age-matched controls showed consistently lower CXCR1 expression in the patients (P = 0.0269; Table ).


Interleukin 8 receptor deficiency confers susceptibility to acute experimental pyelonephritis and may have a human counterpart.

Frendéus B, Godaly G, Hang L, Karpman D, Lundstedt AC, Svanborg C - J. Exp. Med. (2000)

Defective CXCR1 surface expression on neutrophils from children with acute pyelonephritis. (a) CXCR1 receptor expression, quantified by flow cytometry, was reduced in patient 1 (open peak) compared with control 1 (filled peak; for fluorescence intensity see Table ). CXCR2 receptor expression did not differ between the patient and control samples. The dotted line shows the background fluorescence of the IgG control Ab. (b) Confocal images illustrating the difference in neutrophil CXCR1 expression between neutrophils from patient 1 (top left) and control 1 (top right). There was no difference in CXCR2 expression between the patient and the control cells (bottom panels). (c) Decreased CXCR1 mRNA in neutrophils from children with acute pyelonephritis. CXCR1 mRNA was quantified by the RNA protection assay. Samples from patients (P1, P2–P8) or controls (C1, C2–C8) were loaded in alternate wells. CXCR1 mRNA was reduced in all of the patients compared with the controls. The bottom two lanes show mRNA for the housekeeping genes L32 and GAPDH. Data are summarized in Table .
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2193279&req=5

Figure 6: Defective CXCR1 surface expression on neutrophils from children with acute pyelonephritis. (a) CXCR1 receptor expression, quantified by flow cytometry, was reduced in patient 1 (open peak) compared with control 1 (filled peak; for fluorescence intensity see Table ). CXCR2 receptor expression did not differ between the patient and control samples. The dotted line shows the background fluorescence of the IgG control Ab. (b) Confocal images illustrating the difference in neutrophil CXCR1 expression between neutrophils from patient 1 (top left) and control 1 (top right). There was no difference in CXCR2 expression between the patient and the control cells (bottom panels). (c) Decreased CXCR1 mRNA in neutrophils from children with acute pyelonephritis. CXCR1 mRNA was quantified by the RNA protection assay. Samples from patients (P1, P2–P8) or controls (C1, C2–C8) were loaded in alternate wells. CXCR1 mRNA was reduced in all of the patients compared with the controls. The bottom two lanes show mRNA for the housekeeping genes L32 and GAPDH. Data are summarized in Table .
Mentions: Neutrophil CXCR1 receptor expression was low in children with pyelonephritis compared with the age-matched controls (P < 0.03). This is exemplified in Fig. 6 a for patient 1 and control 1. By confocal microscopy, fewer CXCR1+ cells were observed in the patients than in the controls (Fig. 6 b), and flow cytometry showed reduced CXCR1 fluorescence intensity of the patient neutrophils compared with the controls. Pairwise analysis of CXCR1 expression on neutrophils from 12 patients with recurrent pyelonephritis and 12 age-matched controls showed consistently lower CXCR1 expression in the patients (P = 0.0269; Table ).

Bottom Line: Neutrophils migrate to infected mucosal sites that they protect against invading pathogens.The experimental UTI model demonstrated that IL-8R-dependent mechanisms control the urinary tract defense, and that neutrophils are essential host effector cells.The results provide a first molecular clue to disease susceptibility of patients prone to acute pyelonephritis.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Immunology, and Glycobiology, Institute of Laboratory Medicine, Lund University, S-223 62 Lund, Sweden.

ABSTRACT
Neutrophils migrate to infected mucosal sites that they protect against invading pathogens. Their interaction with the epithelial barrier is controlled by CXC chemokines and by their receptors. This study examined the change in susceptibility to urinary tract infection (UTI) after deletion of the murine interleukin 8 receptor homologue (mIL-8Rh). Experimental UTIs in control mice stimulated an epithelial chemokine response and increased chemokine receptor expression. Neutrophils migrated through the tissues to the epithelial barrier that they crossed into the lumen, and the mice developed pyuria. In mIL-8Rh knockout (KO) mice, the chemokine response was intact, but the epithelial cells failed to express IL-8R, and neutrophils accumulated in the tissues. The KO mice were unable to clear bacteria from kidneys and bladders and developed bacteremia and symptoms of systemic disease, but control mice were fully resistant to infection. The experimental UTI model demonstrated that IL-8R-dependent mechanisms control the urinary tract defense, and that neutrophils are essential host effector cells. Patients prone to acute pyelonephritis also showed low CXC chemokine receptor 1 expression compared with age-matched controls, suggesting that chemokine receptor expression may also influence the susceptibility to UTIs in humans. The results provide a first molecular clue to disease susceptibility of patients prone to acute pyelonephritis.

Show MeSH
Related in: MedlinePlus