Cytokines, Adhesion Molecules, and Cellular Infiltration in Nephropathia Epidemica Kidneys: An Immunohistochemical Study

Temonen, Mari; Mustonen, Jukka; Helin, H; Pasternack, Amos; Vaheri, Antti; Holthöfer, Harry

doi:10.1006/clin.1996.0007

Cited by 164 publications

(155 citation statements)

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“…An increased expression of tumour necrosis factor-á (TNF-á), transforming growth factor-â and platelet-derived growth factor are seen at the sites of the maximal in¯ammatory in®ltration of the kidneys of patients with NE [112]. Venous plasma of HFRS patients has been shown to have elevated TNF-á, soluble TNF receptors, interleukin (IL)-6 and IL-10 [104].…”

Section: Pathogenesismentioning

confidence: 99%

Hantaviruses

McCAUGHEY¹,

Hart

2000

Journal of Medical Microbiology

111

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Section: Pathogenesismentioning

confidence: 99%

Hantaviruses

McCAUGHEY¹,

Hart

2000

Journal of Medical Microbiology

111

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“…These molecules limit PUUV replication in humans and in cell cultures (Kanerva et al, 1996;Temonen et al, 1996;Jin et al, 2001). The overproduction of these molecules also leads to pathological symptoms (Li and Youssoufian, 1997;Wenzel et al, 2005;Porter et al, 2006;Bradley, 2008).…”

Section: Introductionmentioning

confidence: 99%

Landscape features and helminth co-infection shape bank vole immunoheterogeneity, with consequences for Puumala virus epidemiology

et al. 2013

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Heterogeneity in environmental conditions helps to maintain genetic and phenotypic diversity in ecosystems. As such, it may explain why the capacity of animals to mount immune responses is highly variable. The quality of habitat patches, in terms of resources, parasitism, predation and habitat fragmentation may, for example, trigger trade-offs ultimately affecting the investment of individuals in various immunological pathways. We described spatial immunoheterogeneity in bank vole populations with respect to landscape features and co-infection. We focused on the consequences of this heterogeneity for the risk of Puumala hantavirus (PUUV) infection. We assessed the expression of the Tnf-a and Mx2 genes and demonstrated a negative correlation between PUUV load and the expression of these immune genes in bank voles. Habitat heterogeneity was partly associated with differences in the expression of these genes. Levels of Mx2 were lower in large forests than in fragmented forests, possibly due to differences in parasite communities. We previously highlighted the positive association between infection with Heligmosomum mixtum and infection with PUUV. We found that Tnf-a was more strongly expressed in voles infected with PUUV than in uninfected voles or in voles co-infected with the nematode H. mixtum and PUUV. H. mixtum may limit the capacity of the vole to develop proinflammatory responses. This effect may increase the risk of PUUV infection and replication in host cells. Overall, our results suggest that close interactions between landscape features, co-infection and immune gene expression may shape PUUV epidemiology.

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“…18 -20 Electron microscopy studies of HFRS, including our analysis, fail to provide convincing evidence of the presence of hantavirus particles in kidney tissue. This may be due to a low amount of hantaviruses in the kidney 21 : In our fatal cases of HFRS, Dobrava hantavirus RNA was detected only in autopsy samples of kidney medulla by highly sensitive reverse transcriptase-PCR and identified by nucleotide sequence analysis. Our study of low-level infection provides evidence that more or less the whole peripheral vascular bed of the kidney, including glomerular and cortical peritubular capillaries, is involved in hantavirus nephropathy; however, by far the most severe vascular affection is in the outer medulla, particularly the outer stripe, presenting in early phases with congestion and permeability disturbances, and from transition to the oliguric phase with severe blood stasis accompanied by leakage, extensive interstitial hemorrhage, severe endothelial degenerative changes, and occasionally anemic necrosis in the deeper medulla.…”

Section: Pathologymentioning

confidence: 79%

“…11,13,15,16,22 In line with our results of cell immunophenotyping, CTL and macrophages are the predominant interstitial inflammatory cells. 21 The histomorphologic features of hantavirus nephropathy are characteristic and diagnostic by renal biopsy when an adequate sample of outer medulla is available. There are only a few other viral PATHOPHYSIOLOGY of the RENAL BIOPSY www.jasn.org hemorrhagic fevers and viral interstitial nephritides in which hemorrhages in the kidney have been reported, and they do not have the same histotopography as HFRS.…”

Section: Pathologymentioning

confidence: 99%

Hantavirus Nephropathy

Ferluga

Vizjak

2008

Journal of the American Society of Nephrology

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A 30-yr-old man was admitted to hospital with a 5-d history of flu-like symptoms: Headache, shivers, nausea, vomiting, backache, arthralgias, myalgias, and blurred vision. In the previous month, he had been in close contact with rodents in the village of Dobrava, which is endemically infested with two hantavirus strains, Puumala and Dobrava. 1 On admission, he was hypotensive with a BP of 85/55 mmHg and a serum creatinine level of 382 mol/L (normal range 44 to 97 mol/ L). On day 6, he became oliguric, somnolent, tachypnic, and tachycardic. Physical examination revealed eyelid edema and conjunctival injections with hemorrhages. Laboratory examination disclosed a 21,600/mm 3 white blood cell count. A platelet count of 34,000/ mm 3 , increased partial thromboplastin time of 65.7 s, and fibrin degradation products of 24.0 mg/L (normal range Ͻ1 mg/L) suggested disseminated intravascular coagulation. Urinalysis showed 1.3 g/d proteinuria and erythrocytes too numerous to count. Severe oliguria persisted, serum creatinine rose on day 7 to 640 mol/L, and on day 9 the patient started hemodialysis for 6 consecutive days. His urine output gradually rose, and he became polyuric during the third week of illness. The patient recovered and was discharged after 4 wk of hospitalization with all laboratory findings normalized except for a slightly increased serum creatinine level of 115 mol/L and mild hematuria. Serologic tests performed on days 6 and 19 revealed a more than four-fold increase in IgG titers by immunofluorescence assay and in IgM titers by capture ELISA using antigens prepared from Vero E6 cells infected with Hantaan strain 76-118, Seoul strain SR-11, Puumala strain Hällnäs B, or Dobrava prototype strain 3970. 1 Acute Puumala infection was confirmed by focus reduction neutralization test, the most sensitive means available for differentiating hantaviruses. 2 Light microscopy of a needle renal biopsy on day 10, encompassing the outer medulla and cortex and containing 11 glomeruli, showed features of mild to moderate acute tubular injury in the cortex, approximately 40% interstitial edema, and scattered, predominantly mononuclear cell infiltrates ( Figure 1A). Electron microscopy disclosed discrete peritubular capillary injury with an effusion of plasma fluid and recent and late extravasation of erythrocytes into the interstitium ( Figure 1B). Glomerular capillaries revealed some swelling of endothelia with reduced fenestrations and scarce subendothelial edema, in line with traces of glomerular IgM found by immunofluorescence. In the biopsy cylinder of the outer medulla, histomorphologic changes were much more pronounced and characteristically dominated by extensive interstitial hemorrhage ( Figure 1A). Compressed floating tubuli and barely visible outlines of congested peritubular capillaries could be seen in a sea created mostly by massive extrusion of erythrocytes, with only a sparse mix of inflammatory cells ( Figure 1A, inset). Focal tubular dilation and discrete damage to tubuli and peritubular capillaries wer...

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Cytokines, Adhesion Molecules, and Cellular Infiltration in Nephropathia Epidemica Kidneys: An Immunohistochemical Study

Cited by 164 publications

References 0 publications

Hantaviruses

Hantaviruses

Landscape features and helminth co-infection shape bank vole immunoheterogeneity, with consequences for Puumala virus epidemiology

Hantavirus Nephropathy

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