Octacalcium phosphate crystals induce inflammation in vivo through interleukin‐1 but independent of the NLRP3 inflammasome in mice

Abstract

Objective. To determine the mechanisms involved in inflammatory responses to octacalcium phosphate (OCP) crystals in vivo.Methods. OCP crystal-induced inflammation was monitored using a peritoneal model of inflammation in mice with different deficiencies affecting interleukin-1 (IL-1) secretion (IL-1␣ -/-, IL-1␤ -/-, ASC -/-, and NLRP3 Conclusion. These data indicate that macrophages, rather than mast cells, are important for initiating and driving OCP crystal-induced inflammation. Additionally, OCP crystals induce IL-1-dependent peritoneal inflammation without requiring the NLRP3 inflammasome.Basic calcium phosphate (BCP) crystals including hydroxyapatite, carbonated apatite, tricalcium phosphate, and octacalcium phosphate (OCP) have long been associated with rheumatic syndromes. BCP crystal deposition occurs most frequently in soft tissue, muscle, and articular sites and can manifest with acute inflammation and tissue degradation. Indeed, the presence of BCP crystals in synovial fluid is more common in

Basic Calcium Phosphate Crystals Induce Monocyte/Macrophage IL-1β Secretion through the NLRP3 Inflammasome In Vitro

“…We have also observed in neutrophil-predominant inflammatory responses induced by i.p. OCP crystals injection that neutrophil recruitment was IL-1-dependent but mainly NLRP3 inflammasome independent (38). We hypothesize that NLRP3 inflammasome activation may play a dominant role in a macrophage-dependent inflammation model but a limited role in neutrophilic inflammation.…”

Cholesterol crystals activate Syk and PI3 kinase in human macrophages and dendritic cells

“…It has previously been shown that serum levels of S100A8/S100A9 are increased in a BCP crystal-induced peritonitis model [19]. Studies from our laboratory have also demonstrated that these particulates can directly induce the up-regulation of S100A8 in primary murine macrophages [12].…”

NLRP3 inflammasome plays a critical role in the pathogenesis of hydroxyapatite-associated arthropathy

“…While this manuscript was in preparation, a recent study was published which showed the involvement of the NLRP3 inflammasome in basic calcium phosphate crystal-induced IL-1β secretion in vitro (34). However, an in vivo study by the same group did not reveal an effect of the inflammasome on octacalcium phosphate crystal-induced murine peritonitis (35). Using primary macrophages and experimental models of arthritis, both our in vitro and in vivo data presented here clearly identify the NLRP3 inflammasome as an essential player that mediates the pathological response to HA crystals by activating caspase-1 and resulting in the secretion of IL-1β and IL-18.…”