Work

Monocyte-macrophage sensing of calciprotein particles in CKD-associated vascular calcification: lysosomal stress and inflammasome activation

Year: 2026

Type: article

Abstract: Chronic kidney disease (CKD) exposes the circulation to sustained calcium-phosphate stress. Calciprotein particles (CPPs) buffer mineral supersaturation and, alongside mineral and bone disorder, uremic toxins, oxidative stress, and inflammation, are an important potential contributor to vascular injury. This mini-review examines how monocytes and macrophages recognize and process CPPs, with emphasis on lysosomal stress and inflammatory responses. Scavenger receptor A contributes to the uptake of mature CPPs in experimental models. In human monocytes studied under high-calcium conditions relevant to rheumatoid arthritis, the calcium-sensing receptor enhances macropinocytosis and CPP uptake. Subsequent responses vary with particle preparation, dose, cell type, and priming. Reported effects include altered lysosomal acidification and proteolysis, and membrane damage in selected models. Genetic and pharmacological studies support the activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome and the release of caspase-1-dependent interleukin-1β. Interleukin-1α release and necrotic injury can persist independently of this pathway. Separate vascular studies have reported endothelial dysfunction and smooth muscle cell calcification after CPP exposure, but have not established that myeloid CPP sensing mediates these effects in CKD. Particle heterogeneity and non-equivalent assays limit the ability to make comparisons across studies. Interventions that reduce mineral loading or delay CPP maturation affect some particle-related measures, but their effects on clinical vascular outcomes remain uncertain.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2026.1982842

Authors: Zhiqiang Xu, Yuying Jiang, Kangwei Wang, Zehao Jin

Institutions: Wenzhou Medical University, Taizhou Central Hospital, Technical University of Munich

Language: English

Topic: Parathyroid Disorders and Treatments

Subfield: Nephrology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801