The interaction of monoclinic calcium pyrophosphate dihydrate crystals with neutrophils

Abstract

Monoclinic calcium pyrophosphate dihydrate (m-CPPD) crystals were synthesized and characterized using physical methods, IgG binding to m-CPPD crystals was quantitated, and the effect of IgG or plasma opsonization on m-CPPD-induced neutrophil activation was determined. Adsorption of IgG to crystals was measured using fluorescent-labelled FITC-IgG. Neutrophil activation by uncoated m-CPPD and crystals precoated with IgG or plasma was measured using luminol-enhanced chemiluminescence, superoxide anion generation, and myeloperoxidase release. m-CPPD bound small (compared to triclinic CPPD) but significant amounts of IgG and induced a strong activation of neutrophils at low concentrations of crystals. The rate and extent of chemiluminescence, superoxide anion production, and degranulation was not affected by precoating m-CPPD crystals with IgG during the early phase of neutrophil responses, but was inhibited by the precoating of crystals with plasma.

Inflammatory Potential of Four Different Phases of Calcium Pyrophosphate Relies on NF-κB Activation and MAPK Pathways

“…Because our experiments were performed with serum-free media, the CPP crystal inflammatory properties could essentially depend on their direct interaction with the plasma cell membrane. This hypothesis is further supported by the opposite effect reported with IgG coating on t-CPPD and m-CPPD crystals ( 49 , 50 ). Moreover, direct interactions between crystals and the plasma cell membrane are strongly emphasized by the rapid activation of intracellular calcium mobilization and MAPK signaling pathways that occur within 1 min of crystal incubation ( 27 , 54 ).…”

“…Thus, adsorption of apolipoprotein B on MSU crystals abrogates their inflammatory potential, whereas adsorption of immunoglobulin G (IgG) increases their inflammatory potential ( 46 , 47 ). Similarly, t-CPPD crystals coated with serum proteins or IgG are more inflammatory than are uncoated t-CPPD crystals, whereas m-CPPD crystals coated with IgG are less inflammatory than are uncoated m-CPPD crystals ( 49 , 50 ). Proteins adsorbed on MSU crystals change during inflammatory reaction, which suggests that adsorbed proteins are not strongly bound to the microcrystal surface ( 46 , 47 , 51 ).…”

Kalziumkristalle im Gelenk

“…Diese Aufnahme wird zusätzlich moduliert durch Proteine, die an der Oberfläche der Kristalle adsorbieren und mit den entsprechenden Membranrezeptoren interagieren [57]. Insbesondere das inflammatorische Potenzial von MSU-und CPPD-Kristallen wird entscheidend von dieser Proteinhülle der Kristalle moduliert [58][59][60]. Es wurde gezeigt, dass die Proteine auf dem Kristall sich während einer Entzündung verändern, was darauf schließen lässt, dass die Bindung der adsorbierten Proteine an den Kristall nur schwach ist [59].…”

Crystal structure of monoclinic calcium pyrophosphate dihydrate (m-CPPD) involved in inflammatory reactions and osteoarthritis

“…They could both be detected in non-inflammatory osteoarthritic joints but also appear to induce an inflammatory response during in vivo and in vitro experiments (Roch-Arveiller et al, 1990;Swan et al, 1995). Although the biological events related to the inflammatory potential of CPP crystals have been studied, the chemical and physico-chemical interactions between the crystals and (Roch-Arveiller et al, 1990;Winternitz et al, 1996;Liu et al, 2009). A proposed mechanism, supported by DFT calculation, involves the rupture of lysosome phospholipid membranes in cells, which is induced by pyrophosphate groups on the surface of the crystals; however, the biological effects could also depend on the crystal structure of the phases as well as on the morphology of the crystals, much in the same way as for other solid phases (Mandel, 1976;Roch-Arveiller et al, 1990;Swan et al, 1995;Wierzbicki et al, 2003).…”