Logo of annrheumdAnnals of the Rheumatic DiseasesVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
Ann Rheum Dis. 1993 Aug; 52(8): 599–607.
PMCID: PMC1005119

Enhancement of crystal induced neutrophil responses by opsonisation of calcium pyrophosphate dihydrate crystals.


OBJECTIVES--Little is known about the effect on crystal induced neutrophil responses of the opsonisation of calcium pyrophosphate dihydrate (CPPD) (triclinic) crystals with components of serum and plasma. The purpose of this study was to determine the effects of precoating CPPD crystals with plasma, serum, complement depleted serum, and IgG on a full range of crystal induced neutrophil responses (calcium mobilisation, chemiluminescence, superoxide anion production, non-cytolytic lysosomal enzyme release, and leukotriene synthesis). METHODS--Crystals were precoated with IgG, serum, plasma, or complement depleted serum (heated at 56 degrees C), incubated with neutrophils and the responses monitored with time. Measurement of the extent of neutrophil association with crystals was based on monitoring the decrease in fluorescence intensity of supernatants when crystals and diphenylhexatriene labelled neutrophils were allowed to settle under gravity. RESULTS--Precoating CPPD crystals with IgG, plasma, and serum significantly enhanced chemiluminescence, superoxide anion generation, increases in cytosolic free calcium levels, and non-cytolytic lysosomal enzyme release by neutrophils compared with uncoated CPPD crystals. The enhancement of neutrophil responses by crystals coated with complement depleted serum was less pronounced. The increased neutrophil responses induced by CPPD crystals coated with IgG might have been due to the observed increase in the association of IgG coated crystals with neutrophils. CONCLUSIONS--These data show that there is a marked potentiation of all neutrophil responses to IgG, plasma, and serum coated CPPD crystals. It is suggested that the adsorption of synovial fluid proteins, including IgG and C3b, to CPPD crystals in vivo, results in the opsonised crystals becoming a potent neutrophil stimulant and inflammatory agent.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.4M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Schumacher HR, Fishbein P, Phelps P, Tse R, Krauser R. Comparison of sodium urate and calcium pyrophosphate crystal phagocytosis by polymorphonuclear leukocytes. Effects of crystal size and other factors. Arthritis Rheum. 1975 Nov-Dec;18(6 Suppl):783–792. [PubMed]
  • Nagase M, Baker DG, Schumacher HR., Jr Immunoglobulin G coating on crystals and ceramics enhances polymorphonuclear cell superoxide production: correlation with immunoglobulin G adsorbed. J Rheumatol. 1989 Jul;16(7):971–976. [PubMed]
  • Burt HM, Jackson JK, Rowell J. Calcium pyrophosphate and monosodium urate crystal interactions with neutrophils: effect of crystal size and lipoprotein binding to crystals. J Rheumatol. 1989 Jun;16(6):809–817. [PubMed]
  • Woolf AD, Dieppe PA. Mediators of crystal-induced inflammation in the joint. Br Med Bull. 1987 Apr;43(2):429–444. [PubMed]
  • Kozin F, McCarty DJ. Protein binding to monosodium urate monohydrate, calcium pyrophosphate dihydrate, and silicon dioxide crystals. I. Physical characteristics. J Lab Clin Med. 1977 Jun;89(6):1314–1325. [PubMed]
  • Hasselbacher P. Binding of IgG and complement protein by monosodium urate monohydrate and other crystals. J Lab Clin Med. 1979 Oct;94(4):532–541. [PubMed]
  • Terkeltaub R, Tenner AJ, Kozin F, Ginsberg MH. Plasma protein binding by monosodium urate crystals. Analysis by two-dimensional gel electrophoresis. Arthritis Rheum. 1983 Jun;26(6):775–783. [PubMed]
  • Cherian PV, Schumacher HR., Jr Immunochemical and ultrastructural characterization of serum proteins associated with monosodium urate crystals (MSU) in synovial fluid cells from patients with gout. Ultrastruct Pathol. 1986;10(3):209–219. [PubMed]
  • Kozin F, Ginsberg MH, Skosey JL. Polymorphonuclear leukocyte responses to monosodium urate crystals: modification by adsorbed serum proteins. J Rheumatol. 1979 Sep-Oct;6(5):519–526. [PubMed]
  • Abramson S, Hoffstein ST, Weissmann G. Superoxide anion generation by human neutrophils exposed to monosodium urate. Arthritis Rheum. 1982 Feb;25(2):174–180. [PubMed]
  • Rosen MS, Baker DG, Schumacher HR, Jr, Cherian PV. Products of polymorphonuclear cell injury inhibit IgG enhancement of monosodium urate-induced superoxide production. Arthritis Rheum. 1986 Dec;29(12):1473–1479. [PubMed]
  • Terkeltaub R, Curtiss LK, Tenner AJ, Ginsberg MH. Lipoproteins containing apoprotein B are a major regulator of neutrophil responses to monosodium urate crystals. J Clin Invest. 1984 Jun;73(6):1719–1730. [PMC free article] [PubMed]
  • Terkeltaub R, Smeltzer D, Curtiss LK, Ginsberg MH. Low density lipoprotein inhibits the physical interaction of phlogistic crystals and inflammatory cells. Arthritis Rheum. 1986 Mar;29(3):363–370. [PubMed]
  • Burt HM, Jackson JK. Characterization and membranolytic effects of triclinic calcium pyrophosphate dihydrate crystals. J Rheumatol. 1987 Oct;14(5):968–973. [PubMed]
  • Grynkiewicz G, Poenie M, Tsien RY. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed]
  • Burt HM, Jackson JK. Monosodium urate monohydrate crystal induced changes in membrane fluidity: a fluorescence polarization study. J Rheumatol. 1988 Jul;15(7):1144–1151. [PubMed]
  • Simchowitz L, Atkinson JP, Spilberg I. Stimulation of the respiratory burst in human neutrophils by crystal phagocytosis. Arthritis Rheum. 1982 Feb;25(2):181–188. [PubMed]
  • Poubelle PE, De Medicis R, Naccache PH. Monosodium urate and calcium pyrophosphate crystals differentially activate the excitation-response coupling sequence of human neutrophils. Biochem Biophys Res Commun. 1987 Dec 16;149(2):649–657. [PubMed]
  • Hed J, Stendahl O. Differences in the ingestion mechanisms of IgG and C3b particles in phagocytosis by neutrophils. Immunology. 1982 Apr;45(4):727–736. [PMC free article] [PubMed]
  • Lucas M, Solano F. Opposite effect of cytochalasin B on agonist-induced respiratory burst in neutrophils and monocytes. Biochem Pharmacol. 1991 Jul 5;42(2):425–430. [PubMed]
  • Goldstein IM, Roos D, Kaplan HB, Weissmann G. Complement and immunoglobulins stimulate superoxide production by human leukocytes independently of phagocytosis. J Clin Invest. 1975 Nov;56(5):1155–1163. [PMC free article] [PubMed]
  • Blackburn WD, Jr, Heck LW. Neutrophil activation by surface bound IgG is via a pertussis toxin insensitive G protein. Biochem Biophys Res Commun. 1989 Nov 15;164(3):983–989. [PubMed]
  • Fällman M, Lew DP, Stendahl O, Andersson T. Receptor-mediated phagocytosis in human neutrophils is associated with increased formation of inositol phosphates and diacylglycerol. Elevation in cytosolic free calcium and formation of inositol phosphates can be dissociated from accumulation of diacylglycerol. J Clin Invest. 1989 Sep;84(3):886–891. [PMC free article] [PubMed]
  • Della Bianca V, Grzeskowiak M, Lissandrini D, Rossi F. Source and role of diacylglycerol formed during phagocytosis of opsonized yeast particles and associated respiratory burst in human neutrophils. Biochem Biophys Res Commun. 1991 Jun 28;177(3):948–955. [PubMed]
  • Terkeltaub RA, Sklar LA, Mueller H. Neutrophil activation by inflammatory microcrystals of monosodium urate monohydrate utilizes pertussis toxin-insensitive and -sensitive pathways. J Immunol. 1990 Apr 1;144(7):2719–2724. [PubMed]
  • Onello E, Traynor-Kaplan A, Sklar L, Terkeltaub R. Mechanism of neutrophil activation by an unopsonized inflammatory particulate. Monosodium urate crystals induce pertussis toxin-insensitive hydrolysis of phosphatidylinositol 4,5-bisphosphate. J Immunol. 1991 Jun 15;146(12):4289–4294. [PubMed]
  • Bomalaski JS, Baker DG, Brophy LM, Clark MA. Monosodium urate crystals stimulate phospholipase A2 enzyme activities and the synthesis of a phospholipase A2-activating protein. J Immunol. 1990 Nov 15;145(10):3391–3397. [PubMed]

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Group


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem chemical compound records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records. Multiple substance records may contribute to the PubChem compound record.
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...