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Neutrophil extracellular trap components in fibrinoid necrosis of the kidney with myeloperoxidase-ANCA-associated vasculitis.

Yoshida M, Sasaki M, Sugisaki K, Yamaguchi Y, Yamada M - Clin Kidney J (2013)

Bottom Line: In response to antineutrophil cytoplasmic antibody (ANCA), activated neutrophils release decondensed chromatin associated with cytoplasmic granular proteins composed of proteolytic enzymes and myeloperoxidase (MPO); these complexes are named neutrophil extracellular traps (NETs).NET formation requires peptidylarginine deiminase 4 (PAD4) to citrullinate chromatin histones and also MPO and neutrophil elastase to aid in decondensation and release of chromatin.Immunostaining of renal biopsy revealed that NET components of citrullinated histone, MPO and PAD4 were concurrently deposited both around fibrinoid necrosis in necrotizing glomerulonephritis in the early focal phase of ANCA-associated polyangiitis and along an interlobular arterial wall.

View Article: PubMed Central - PubMed

Affiliation: Renal Unit of Internal Medicine , Hachioji Medical Center , Tokyo Medical University , Tokyo , Japan.

ABSTRACT
In response to antineutrophil cytoplasmic antibody (ANCA), activated neutrophils release decondensed chromatin associated with cytoplasmic granular proteins composed of proteolytic enzymes and myeloperoxidase (MPO); these complexes are named neutrophil extracellular traps (NETs). NET formation requires peptidylarginine deiminase 4 (PAD4) to citrullinate chromatin histones and also MPO and neutrophil elastase to aid in decondensation and release of chromatin. Immunostaining of renal biopsy revealed that NET components of citrullinated histone, MPO and PAD4 were concurrently deposited both around fibrinoid necrosis in necrotizing glomerulonephritis in the early focal phase of ANCA-associated polyangiitis and along an interlobular arterial wall.

No MeSH data available.


Related in: MedlinePlus

Immunomicrograph of fibrinoid necrosis of the interlobular artery with the early focal class of MPO-ANCA-associated glomerulonephritis. The view field of necrotizing interlobular artery is shown for the sections described in Figure 1. (A) Periodic acid-Schiff stain; (B) PAD4 stain; (C) citrullinated histone stain; (D) MPO stain. The signals appear concurrently with PAD4, citrullinated histones and MPO, distributed in fibrinoid necrosis of the interlobular artery. A–D: ×20.
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SFT048F3: Immunomicrograph of fibrinoid necrosis of the interlobular artery with the early focal class of MPO-ANCA-associated glomerulonephritis. The view field of necrotizing interlobular artery is shown for the sections described in Figure 1. (A) Periodic acid-Schiff stain; (B) PAD4 stain; (C) citrullinated histone stain; (D) MPO stain. The signals appear concurrently with PAD4, citrullinated histones and MPO, distributed in fibrinoid necrosis of the interlobular artery. A–D: ×20.

Mentions: A 70-year-old man who had a low-grade fever was treated with antibiotics and a nonsteroidal anti-inflammatory drug. About 1 week after a fall, general malaise and peripheral edema appeared. He was admitted to our renal department and his condition was diagnosed as rapidly progressive glomerulonephritis. He had no family history of kidney disease. Physical examination findings included the following: height 160 cm; weight 45 kg; body temperature 37.2°C; blood pressure 137/72 mmHg; edema present in both of the lower legs. The rest of the physical examination was unremarkable. A further clinical workup indicated kidney failure with MPO-ANCA-positive vasculitis, supported by the following laboratory data: serum creatinine 2.19 mg/dL (200 µmol/L), eGFR 23.7 (mL/min/1.73 m2); eGFR (mL/min/1.73 m2) = 194 × serum creatinine−1.094 × age−0.287) [10] urea nitrogen 48.0 mg/dL (19 mmol/L), C-reactive protein 7.39 mg/dL, MPO-ANCA 276 EU (reference <20 EU), negative serologic tests for PR-3-ANCA and anti-glomerular basement membrane antibodies, and urinalysis showed protein (+) and blood (3+). Microscopic examination of urine showed numerous erythrocytes and casts. A percutaneous kidney biopsy was performed 1 day after the admission. In light microscopy, 15 glomeruli were included. The renal specimen shows a fibrinoid necrosis with cellular crescent and apoptosis-like appearance of neutrophils (Figure 1A). Then, the serial sections were immunostained for citrullinated histone using anti-citrullinated histone H3 peptide antibodies [8], for MPO using an antiserum against MPO and for PAD4 using anti-PAD4 antibodies in a coupled reaction with peroxidase-conjugated goat anti-rabbit IgG antibodies (Figure 1B–D). Strong positivities for citrullinated histone, MPO and PAD4 were distributed throughout the foci. The three antibodies were recognized to be distributed in cytoplasmic and extracellular sites, as well as the nuclei of the cells of the foci. More exactly, double immunofluorescence staining of the section revealed the codistribution of significant signals of MPO and citrullinated histone in the fibrinoid necrosis of the cellular crescent in the lesion (Supplementary Figure S1). The three other glomeruli with fibrocellular crescents showed no immunostaining for citrullinated histione, MPO and PAD4 (Figure 2). In the 11 glomeruli showing only minor abnormalities, almost no signals were found throughout the sections. The other view field of the sections exhibited a typical fibrinoid necrosis of the interlobular artery (Figure 3A). Some immunostains for citrullinated histone, MPO and PAD4 were distributed in the extracellular and cytoplasmic sites, as well as in the nuclei, of the cells throughout the lesion (Figure 3B–D). More directly, double immunofluorescence staining of the section indicated the codistribution of MPO and PAD4 in the fibrinoid necrosis of the interlobular artery (Supplementary Figure S2). MPO-AAV was recognized as belonging to the focal class, according to the histopathologic classification [9]. No immunoglobulin or complement deposition was found. Immunostaining of renal biopsy sections from a patient with anti-glomerular basement membrane glomerulonephritis revealed no signals of PAD4, citrullinated histone and MPO in the cellular crescent of glomerulus in the lesion (Supplementary Figure S3). The occurrence of NET components is likely to be specific for a type of renal disease.Fig. 1.


Neutrophil extracellular trap components in fibrinoid necrosis of the kidney with myeloperoxidase-ANCA-associated vasculitis.

Yoshida M, Sasaki M, Sugisaki K, Yamaguchi Y, Yamada M - Clin Kidney J (2013)

Immunomicrograph of fibrinoid necrosis of the interlobular artery with the early focal class of MPO-ANCA-associated glomerulonephritis. The view field of necrotizing interlobular artery is shown for the sections described in Figure 1. (A) Periodic acid-Schiff stain; (B) PAD4 stain; (C) citrullinated histone stain; (D) MPO stain. The signals appear concurrently with PAD4, citrullinated histones and MPO, distributed in fibrinoid necrosis of the interlobular artery. A–D: ×20.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4400491&req=5

SFT048F3: Immunomicrograph of fibrinoid necrosis of the interlobular artery with the early focal class of MPO-ANCA-associated glomerulonephritis. The view field of necrotizing interlobular artery is shown for the sections described in Figure 1. (A) Periodic acid-Schiff stain; (B) PAD4 stain; (C) citrullinated histone stain; (D) MPO stain. The signals appear concurrently with PAD4, citrullinated histones and MPO, distributed in fibrinoid necrosis of the interlobular artery. A–D: ×20.
Mentions: A 70-year-old man who had a low-grade fever was treated with antibiotics and a nonsteroidal anti-inflammatory drug. About 1 week after a fall, general malaise and peripheral edema appeared. He was admitted to our renal department and his condition was diagnosed as rapidly progressive glomerulonephritis. He had no family history of kidney disease. Physical examination findings included the following: height 160 cm; weight 45 kg; body temperature 37.2°C; blood pressure 137/72 mmHg; edema present in both of the lower legs. The rest of the physical examination was unremarkable. A further clinical workup indicated kidney failure with MPO-ANCA-positive vasculitis, supported by the following laboratory data: serum creatinine 2.19 mg/dL (200 µmol/L), eGFR 23.7 (mL/min/1.73 m2); eGFR (mL/min/1.73 m2) = 194 × serum creatinine−1.094 × age−0.287) [10] urea nitrogen 48.0 mg/dL (19 mmol/L), C-reactive protein 7.39 mg/dL, MPO-ANCA 276 EU (reference <20 EU), negative serologic tests for PR-3-ANCA and anti-glomerular basement membrane antibodies, and urinalysis showed protein (+) and blood (3+). Microscopic examination of urine showed numerous erythrocytes and casts. A percutaneous kidney biopsy was performed 1 day after the admission. In light microscopy, 15 glomeruli were included. The renal specimen shows a fibrinoid necrosis with cellular crescent and apoptosis-like appearance of neutrophils (Figure 1A). Then, the serial sections were immunostained for citrullinated histone using anti-citrullinated histone H3 peptide antibodies [8], for MPO using an antiserum against MPO and for PAD4 using anti-PAD4 antibodies in a coupled reaction with peroxidase-conjugated goat anti-rabbit IgG antibodies (Figure 1B–D). Strong positivities for citrullinated histone, MPO and PAD4 were distributed throughout the foci. The three antibodies were recognized to be distributed in cytoplasmic and extracellular sites, as well as the nuclei of the cells of the foci. More exactly, double immunofluorescence staining of the section revealed the codistribution of significant signals of MPO and citrullinated histone in the fibrinoid necrosis of the cellular crescent in the lesion (Supplementary Figure S1). The three other glomeruli with fibrocellular crescents showed no immunostaining for citrullinated histione, MPO and PAD4 (Figure 2). In the 11 glomeruli showing only minor abnormalities, almost no signals were found throughout the sections. The other view field of the sections exhibited a typical fibrinoid necrosis of the interlobular artery (Figure 3A). Some immunostains for citrullinated histone, MPO and PAD4 were distributed in the extracellular and cytoplasmic sites, as well as in the nuclei, of the cells throughout the lesion (Figure 3B–D). More directly, double immunofluorescence staining of the section indicated the codistribution of MPO and PAD4 in the fibrinoid necrosis of the interlobular artery (Supplementary Figure S2). MPO-AAV was recognized as belonging to the focal class, according to the histopathologic classification [9]. No immunoglobulin or complement deposition was found. Immunostaining of renal biopsy sections from a patient with anti-glomerular basement membrane glomerulonephritis revealed no signals of PAD4, citrullinated histone and MPO in the cellular crescent of glomerulus in the lesion (Supplementary Figure S3). The occurrence of NET components is likely to be specific for a type of renal disease.Fig. 1.

Bottom Line: In response to antineutrophil cytoplasmic antibody (ANCA), activated neutrophils release decondensed chromatin associated with cytoplasmic granular proteins composed of proteolytic enzymes and myeloperoxidase (MPO); these complexes are named neutrophil extracellular traps (NETs).NET formation requires peptidylarginine deiminase 4 (PAD4) to citrullinate chromatin histones and also MPO and neutrophil elastase to aid in decondensation and release of chromatin.Immunostaining of renal biopsy revealed that NET components of citrullinated histone, MPO and PAD4 were concurrently deposited both around fibrinoid necrosis in necrotizing glomerulonephritis in the early focal phase of ANCA-associated polyangiitis and along an interlobular arterial wall.

View Article: PubMed Central - PubMed

Affiliation: Renal Unit of Internal Medicine , Hachioji Medical Center , Tokyo Medical University , Tokyo , Japan.

ABSTRACT
In response to antineutrophil cytoplasmic antibody (ANCA), activated neutrophils release decondensed chromatin associated with cytoplasmic granular proteins composed of proteolytic enzymes and myeloperoxidase (MPO); these complexes are named neutrophil extracellular traps (NETs). NET formation requires peptidylarginine deiminase 4 (PAD4) to citrullinate chromatin histones and also MPO and neutrophil elastase to aid in decondensation and release of chromatin. Immunostaining of renal biopsy revealed that NET components of citrullinated histone, MPO and PAD4 were concurrently deposited both around fibrinoid necrosis in necrotizing glomerulonephritis in the early focal phase of ANCA-associated polyangiitis and along an interlobular arterial wall.

No MeSH data available.


Related in: MedlinePlus