Tumors of the Urinary System

10. Tumors of the Urinary System

Neutrophils, the most abundant white blood cells in humans, are critical for host defense against invading pathogens. Equipped with an array of antimicrobial molecules, neutrophils can eradicate bacteria and clear debris. Among the microbicide proteins is the heme protein myeloperoxidase (MPO), stored in the azurophilic granules, and catalyzes the formation of the chlorinating oxidant HOCl and other oxidants (HOSCN and HOBr). MPO is generally associated with killing trapped bacteria and inflicting collateral tissue damage to the host. However, the characterization of non-enzymatic functions of MPO suggests additional roles for this protein. Indeed, evolving evidence indicates that MPO can directly modulate the function and fate of neutrophils, thereby shaping immunity. These actions include MPO orchestration of neutrophil trafficking, activation, phagocytosis, lifespan, formation of extracellular traps, and MPO-triggered autoimmunity. This review scrutinizes the multifaceted roles of MPO in immunity, focusing on neutrophil-mediated host defense, tissue damage, repair, and autoimmunity. We also discuss novel therapeutic approaches to target MPO activity, expression, or MPO signaling for the treatment of inflammatory and autoimmune diseases.

/pdf/myeloperoxidase-regulation-of-neutrophil-function-and-target-2oomesh6.pdf

Myeloperoxidase: Regulation of Neutrophil Function and Target for Therapy

Summary Neutrophils were long considered to be a short-lived homogenous cell population, limited to their role as first responders in anti-bacterial and -fungal immunity. While it is true that neutrophils are first to infiltrate the site of infection to eliminate pathogens, growing evidence suggests their functions could extend beyond those of basic innate immune cells. Along with their well-established role in pathogen elimination, utilizing effector functions such as phagocytosis, degranulation, and the deployment of neutrophil extracellular traps (NETs), neutrophils have recently been shown to possess antigen-presenting capabilities. Moreover, the identification of different subtypes of neutrophils points to a multifactorial heterogeneous cell population with great plasticity in which some subsets have enhanced pro-inflammatory characteristics, while others seem to behave as immunosuppressors. Interestingly, the aberrant presence of activated neutrophils with a pro-inflammatory profile in several systemic and organ-specific autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), multiple sclerosis (MS), and type 1 diabetes (T1D) could potentially be exploited in novel therapeutic strategies. The full extent of the involvement of neutrophils, and more specifically that of their various subtypes, in the pathophysiology of autoimmune diseases is yet to be elucidated.

/pdf/neutrophils-in-autoimmunity-when-the-hero-becomes-the-2xwqs3gm.pdf

Neutrophils in autoimmunity: when the hero becomes the villain

A nephroblastoma consisting predominantly of mature mesenchymal components developed in a 7-month-old male beagle dog. The dog was necropsied after experimental use. There were no abnormal signs or laboratory tests prior to necropsy. The left kidney was slightly enlarged, and the tumorous area of the kidney was gray-white. The cut surface of the tumor, occupying the upper one-third of the kidney, revealed a solid, rubbery, yellow-white mass. The tumor was about 3.0 cm in its greatest diameter, showed replacement growth pattern, and lacked a capsule (Fig. 1). Histologically, the tumor was mainly composed of spindle cells arranged in interlacing bundles that were intermingled with the normal renal tissue; however, there was no sharp demarcation between bundles and the surrounding renal parenchyma. The greater part of the tumor had a loose myxomatous pattern with an alcian blue-positive matrix, but dense, cellular, fibromatous areas with transition to the myxomatous areas were also noted (Fig. 2). Spindle cells (fibroblasts) had scanty cytoplasm with cigar-shaped nuclei and were negative for phosphotungstic acid-hematoxylin staining. Neither nuclear atypia nor mitotic figures were detected. Within the myxomatous area, cysts of various sizes were recognized in addition to entrapped nephrons. The small cysts were dilated

https://journals.sagepub.com/doi/pdf/10.1177/030098588902600316

Congenital mesoblastic nephroma in a dog: a benign variant of nephroblastoma.

Abstract The ANCA associated vasculitides (AAVs) affect a range of internal organs including ear nose and throat, respiratory tract, kidneys, skin and nervous system. They include granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA) and microscopic polyangiitis (MPA). The AAVs are treated with high dose glucocorticoids, immunosuppressants, and targeted biological medications. Since the 1990s classification criteria for the AAVs have been based on clinical features, laboratory tests and basic imaging; an initiative to update the classification criteria incorporating newer tests, for example, anti-neutrophil cytoplasmic antibodies (ANCA) and novel imaging techniques will be published this year. There is also evidence for classification of patients based on ANCA subtype; those with anti-proteinase 3 antibodies (PR3) or anti-myeloperoxidase antibodies (MPO) have differences in response to treatment and clinical outcomes. An update is described within this review. The pathogenesis of AAV involves necrotizing inflammation of small to medium blood vessels involving multiple immunological pathways. We present an update on emerging evidence related to auto-antibodies, complement and lymphocyte pathways. This review describes emerging treatment regimens, including evidence for plasma exchange in severe disease and the inhibitor of the complement C5a receptor (C5aR) inhibitor, Avacopan. Lastly, patient reported outcomes are key secondary outcomes in randomised controlled trials and increasingly clinical practice, we report development in disease specific and glucocorticoid-specific PROs.

ANCA Associated Vasculitis Subtypes: Recent Insights and Future Perspectives

https://journals.sagepub.com/doi/pdf/10.1177/030098588602300112

Renal Interstitial Cell Tumors in the Dog

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