Calcium Oxalate Differentiates Human Monocytes Into Inflammatory M1 Macrophages

Abstract

PurposeA number of hyperoxaluric states have been associated with calcium oxalate (CaOx) deposits in the kidneys. In animal models of stone disease, these crystals interact with circulating monocytes that have migrated into the kidney as part of innate immunity. Similarly, macrophages surround CaOx crystals in kidneys of patients excreting high levels of oxalate. We investigate the effect of this exposure and subsequent human immunological response in vitro.Materials and methodsPrimary human monocytes were collected from healthy donors and exposed to CaOx, potassium oxalate, and zinc oxalate (ZnOx). Cytokine production was measured with a multiplex ELISA. Quantitative reverse transcription-polymerase chain reaction was done to validate the mRNA profile expression. M1 macrophage phenotype was confirmed with immunofluorescence microscopy.ResultsBoth primary monocytes and THP-1 cells, a human monocytic cell line, respond strongly to CaOx crystals in a dose-dependent manner producing TNF-α, IL-1β, IL-8, and IL-10 transcripts. Exposure to CaOx followed by 1 h with LPS had an additive effect for cytokine production compared to LPS alone, however, LPS followed by CaOx led to significant decrease in cytokine production. Supernatants taken from monocytes were previously exposed to CaOx crystals enhance M2 macrophage crystal phagocytosis. CaOx, but not potassium or ZnOx, promotes monocyte differentiation into inflammatory M1-like macrophages.ConclusionIn our in vitro experiment, human monocytes were activated by CaOx and produced inflammatory cytokines. Monocytes recognized CaOx crystals through a specific mechanism that can enhance or decrease the innate immune response to LPS. CaOx promoted M1 macrophage development. These results suggest that monocytes have an important role promoting CaOx-induced inflammation.

LncRNA HOXA11‐AS regulates calcium oxalate crystal–induced renal inflammation via miR‐124‐3p/MCP‐1

“…The excessive ROS can then activate the NF‐κB, NLRP3, NACHT and LRR inflammatory pathways, leading to the secretion of many inflammatory factors such as OPN, MCP‐1, CD44, TGF‐β and IL‐1β, among others . Successively, monocytes are chemotactically attracted by chemokines and converge to inflammatory sites where the monocyte can be activated to macrophages by COM and inflammatory cytokines and, thus, secrete more proinflammatory cytokines, followed by the enhancement of vasopermeability, recruitment of additional inflammatory cells, activation of complement and initiation of renal fibrosis . Therefore, the inflammatory response is amplified by this amplificatory loop, thereby aggravating kidney damage, which is conducive to stone formation.…”

“…4,5 Successively, monocytes are chemotactically attracted by chemokines and converge to inflammatory sites where the monocyte can be activated to macrophages by COM and inflammatory cytokines and, thus, secrete more proinflammatory cytokines, followed by the enhancement of vasopermeability, recruitment of additional inflammatory cells, activation of complement and initiation of renal fibrosis. 6,[29][30][31] Therefore, the inflammatory response is amplified by this amplificatory loop, thereby aggravating kidney damage, which is conducive to stone formation. It is well known that macrophages are phagocytic cells that can eliminate COM to some extent.…”

Immunophenotypic Profiles in Polycystic Ovary Syndrome

“…A plethora of Ca 2+ -permeable channels in T cells at various locations, with unique activation mechanisms, have been reported to be necessary for T cell activation, maturation, and secretion of cytokines [97]. Not only Ca 2+ can activate human monocytes to produce inflammatory cytokines and promote M1 macrophage development [98], but Ca 2+ influx is also vital in the proinflammatory functions of neutrophils, which promotes autoimmune and Mediators of Inflammation inflammatory disease progression and exacerbates collateral damages to the host tissues [99]. The change and function of Ca 2+ in PCOS still need further research.…”

Submicron Crystals of the Parkinson’s Disease Substantia nigra: Calcium Oxalate, Titanium Dioxide and Iron Oxide

“…particles. Both are phagocytized, [25,[35][36][37][38][39] the TiO2 also by microglia [20,40]. In mice, activation of microglial NLRP3 inflammasome by misfolded α-synuclein causes the death of proximal dopaminergic neurons.…”

“…It is a long-known cytotoxic component of urinary tract and kidney calculi, [30][31][32] associated also with retinopathy. [33,34] Both COD and TiO2 are phagocytized, [25,[35][36][37][38][39] TiO2 also by microglia. [40] Both activate the NLRP3 inflammasome.…”