Histologic Localization of Terminal Complement Complexes in Renal Diseases: An Immunohistochemical Study

Ootaka, Tetsuya; Suzuki, Masahiko; Sudo, Katsuhiko; Sato, Hiroshi; Seino, Jin; Saito, Takao; Yoshinaga, Kaoru

doi:10.1093/ajcp/91.2.144

Cited by 30 publications

(39 citation statements)

References 8 publications

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“…According to these findings, types C and F may represent subentities of IgAN. We have not found any literature on IgAN referring to this dissociation although the report by Tomino and Sakai [27] and our previous report [20] strongly suggested this evidence.…”

Section: Discussionmentioning

confidence: 58%

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Mechanism of Infiltration and Activation of Glomemlar Monocytes/Macrophages in IgA Nephropathy

et al. 1997

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Glomemlar deposits of fibrin-related antigens (FRA), C3c, membrane attack complex (MAC) were examined by the immunoperoxidase method on 176 renal biopsy specimens from 120 cases with IgA nephropathy including 56 cases with sequential biopsies. On 47 sets of repeated renal biopsy specimens, the glomemlar infiltration of the following immune cells was examined by the indirect immunoperoxidase method; immune cells positive for C3bi receptor (C3biR; CR3/CDllb, CR4/CDllc), HLADR antigen and several leukocyte surface markers (CD45R, CD3, CD 15 and CD68). Twenty-four-hour urine protein (UP) at the renal biopsy was also evaluated. The glomemlar deposition of FRA was inversely correlated with C3c/MAC deposition (p < 0.00001). Most cases (163 of 176) were classified into the following two types; type C with dominant deposition of C3c (97 cases) and type F with dominant deposition of FRA (66 cases), except for 13 cases with equivalent deposits of C3c and FRA (7 cases, type B) and without C3 or FRA deposits (6 cases, type O). In 56 rebiopsied cases, apparent conversion from type F or C into the other was observed only in one case though a few cases in type C lost or reduced C3c deposition to an equivocal type at the follow-up biopsy, which were included in type C, an expanded category of type C. In the whole cases, the glomemlar infiltration of immune cells was significantly correlated with FRA deposition (p < 0.0002) but not with C3c. Glomemlar CDl lc+ cells were significantly correlated with C3c deposition in type C (p < 0.0001), but not in type F. Glomemlar HLADR positive immune cells were significantly correlated with glomemlar CD3+ T cells in type F (p < 0.001), but not in type C. In type C, UP was significantly correlated with glomemlar CDl lc+ cells (p < 0.0001) but not with CD 15+ or HLADR+ cells. On the other hand, in type F, UP was significantly correlated with CDl 5+ and HLADR+ cells (p < 0.001) but not with CDl lc+ cells. These results suggested that there are multiple pathways in inducing glomer-ular infiltration of immune cells in IgA nephropathy. In type C, local activation of complements might primarily induce immune cell infiltration through C3biR and these C3biR+ cells are involved in inducing proteinuria. On the other hand, in type F, in which complement activation is weak, immune cells might infiltrate directly through their Fc receptor or MHC class II antigens, and might be activated by T-cell/macrophage interaction to induce proteinuria.

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Section: Discussionmentioning

confidence: 58%

“…Immunohistological staining for immune deposits was performed for all patients by the 2-layer indirect immunoperoxidase method as previously described [19,20], Staining intensities of glomerular deposits were scored on a semiquantitative scale from -to +++.…”

Section: Immunohistological Stainingmentioning

confidence: 99%

Mechanism of Infiltration and Activation of Glomemlar Monocytes/Macrophages in IgA Nephropathy

et al. 1997

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“…Sublethal complement activation occurs on affected podocytes, causing damage and intracellular signaling activation (162,35). It has been well documented that deposition of the terminal components of complement (c5b-9) occurs not only in PHN (3,33,82,135,147) but also in MN in humans (30,49,91,131,133). Moreover, c5b-9 is required in some models of PHN (9,34,124,135).…”

Section: Rat Model Of Passive Heymann Nephritismentioning

confidence: 99%

Inducible rodent models of acquired podocyte diseases

Pippin

Brinkkoetter²,

Cormack-Aboud³

et al. 2009

American Journal of Physiology-Renal Physiology

236

263

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Pippin JW, Brinkkoetter PT, Cormack-Aboud FC, Durvasula RV, Hauser PV, Kowalewska J, Krofft RD, Logar CM, Marshall CB, Ohse T, Shankland SJ. Inducible rodent models of acquired podocyte diseases. Am J Physiol Renal Physiol 296: F213-F229, 2009. First published September 10, 2008 doi:10.1152/ajprenal.90421.2008.-Glomerular diseases remain the leading cause of chronic and end-stage kidney disease. Significant advances in our understanding of human glomerular diseases have been enabled by the development and better characterization of animal models. Diseases of the glomerular epithelial cells (podocytes) account for the majority of proteinuric diseases. Rodents have been extensively used experimentally to better define mechanisms of disease induction and progression, as well as to identify potential targets and therapies. The development of podocyte-specific genetically modified mice has energized the research field to better understand which animal models are appropriate to study acquired podocyte diseases. In this review we discuss inducible experimental models of acquired nondiabetic podocyte diseases in rodents, namely, passive Heymann nephritis, puromycin aminonucleoside nephrosis, adriamycin nephrosis, liopolysaccharide, crescentic glomerulonephritis, and protein overload nephropathy models. Details are given on the model backgrounds, how to induce each model, the interpretations of the data, and the benefits and shortcomings of each. Genetic rodent models of podocyte injury are excluded.glomerulus; animal models HISTOLOGICAL ANALYSIS is a cornerstone for studying mechanisms of glomerular disease. However, analysis in human disease is limited by a relative paucity of tissue availability. Renal biopsies are only pursued if a presumptive diagnosis cannot be established on clinical grounds. Tissue sampling is typically restricted to the time of disease presentation and is rarely performed in follow-up, providing a mere snapshot of disease course.Animal models have significantly advanced our understanding of the pathogenesis of glomerular disease by overcoming these hurdles. Serial assessment of renal tissue in experimental models affords the opportunity to study development and progression of disease over time. Furthermore, the host response to injury may be deliberately modified, for example, through pharmacological intervention, selective disruption (knockout strategies), or overexpression (transgenic strategies) of a particular gene, allowing for mechanistic evaluations. A variety of animal species have been employed in the study of glomerular disease, but rodent models are preferred due to lower cost, maintenance requirements, and short gestational periods. Although both rats and mice are utilized, there are some important advantages and disadvantages for each (Table 1). The development of transgenic technology has proven an invaluable tool in elucidating the function of individual genes in health and disease. However, they cannot replace experimental models in furthering our understanding of the mechanisms...

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“…The extent of glomerular damage was evaluated using the index of glomerular lesions (IGL) according to the method originally pro posed by Suwa and Takahashi [16] with a modification to evaluate sclerotic changes as previously described [13,[17][18][19][20][21]. No + N| + Ns + Nj + N4…”

Section: Index O F Glomerular Lesionsmentioning

confidence: 99%

“…The intervals between renal biopsy and tonsillectomy in cases 7-10 were 15 days to 2 months and 2 years and 4 months in case 12. The correlation between IGI.and the percentage of the nonreticulated area in tonsils of 10 cases of IgAN (cases 1-10) and 12 controls (eases [15][16][17][18][19][20][21][22][23][24][25][26] are shown in figure 5. Since control patients had normal renal functions, with no history of renal, hepatic or systemic diseases, we esti mated that their IGL would be zero.…”

Section: Positive Correlation Betw Een Igl and Area O F Nonreticulatementioning

confidence: 99%

IgA Nephropathy with Poorly Developed Lymphoepithelial Symbiosis of the Palatine Tonsils

Hasegawa

Taguma

Takasaka

et al. 1996

Nephron

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Tonsillar abnormalities have been observed in patients with IgA nephropathy (IgAN). In addition, it has been suggested that reticulization of tonsillar crypt epithelium is important in tonsillar immunity. Therefore, we investigated reticulization of this area in patients with IgAN (14 cases) and compared results with those of control patients who exhibited recurrent tonsillitis or tonsillar hypertrophy (12 cases). Immunohistochemical staining of antikeratin antibody PKK1 was employed to visualize reticulization. Tonsils of controls showed well developed reticular crypt epithelia with lymphoepithelial symbiosis and the nonreticulated area was less than 7% of the total crypt epithelia per overall section. In IgAN tonsils, however, nonreticulated crypt epithelium was frequently observed and, in the advanced stage of IgAN, exceeded 50% of total crypt epithelia. The extent of glomerular damage in IgAN patients correlated significantly with the percentage of the area of nonreticulated crypt in palatine tonsils with a correlation coefficient of 0.91. Considered together with our finding that PKK1 -positive epithelial reticular cells strongly expressed HLA-DR antigens in normal tonsils, the low level of reticulization in IgAN patients may induce the unusual immunity responsible for the pathogenesis of IgAN.

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Histologic Localization of Terminal Complement Complexes in Renal Diseases: An Immunohistochemical Study

Cited by 30 publications

References 8 publications

Mechanism of Infiltration and Activation of Glomemlar Monocytes/Macrophages in IgA Nephropathy

Mechanism of Infiltration and Activation of Glomemlar Monocytes/Macrophages in IgA Nephropathy

Inducible rodent models of acquired podocyte diseases

IgA Nephropathy with Poorly Developed Lymphoepithelial Symbiosis of the Palatine Tonsils

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