C3 activation by monosodium urate monohydrate and other crystalline material

Our plain-English summary of C3 activation by monosodium urate monohydrate and other crystalline material, by P. Hasselbacher (Arthritis and Rheumatism, 1979).

The study

• Author: P. Hasselbacher
• Journal: Arthritis and Rheumatism
• Published: 1979;22(6):571-8
• Cited by: 64 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Monosodium urate monohydrate (MSUM) is a potent activator of the complement system as measured by electrophoretic conversion of beta1C to beta1A. Activation of C3 in human serum by MSUM is both time- and dose-dependent. The sensitivity of the assay allows detection of C3 activation by as little as 0.2 mg/ml of MSUM. It was observed that C3 activation is calcium dependent and elimination by both EDTA and EGTA, a finding that demonstrated the major role of the classic pathway of complement activation. Excess calcium or magnesium alone inhibited C3 activation by MSUM in accord with the inhibitory effect of these cations on sensitized sheep cell hemolysis by complement. Heating of MSUM at 200 degrees C for 2 hours removes the water of crystallization such that heated crystals may no longer be considered MSUM. Such treatment has a variable effect on C3 activation. Of the crystals and other material studied, only zymosan was more potent than MSUM in activating C3. Calcium prophosphate dihydrate and hydroxyapatite activated significant amounts of C3. Asbestos, glass wool, or a variety of microcrystalline steroids activated little or no C3.

In plain English

This laboratory study mixed crystals and other materials with fresh serum from one human donor and measured activation of C3, a protein of the complement system. Its main focus was monosodium urate monohydrate (MSUM), a urate crystal linked to gout. MSUM activated C3 more with higher doses and longer incubation, and activation was detected at 0.2 mg/ml. Adding EDTA or EGTA, chemicals that bind calcium, blocked activation by MSUM. The author took this as evidence for the classic pathway of complement activation. In side-by-side tests, MSUM gave a mean excess converted area of 26.5%, exceeded only by zymosan (43%). Calcium pyrophosphate dihydrate gave 11.5%, potassium urate 9.0% and hydroxyapatite 5.3%. Asbestos (described only as amphibole, listed at 14 mg/ml) and glass wool showed little activity, even in larger doses. Of eight steroid preparations, only prednisolone acetate activated significantly more C3 than controls. The author noted that the plastic tubes themselves activated C3 in controls. The author concluded that activation by MSUM is calcium dependent and occurs through the classic pathway.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) experiment measuring C3 activation in human serum by crystals and other materials, using crossed immunoelectrophoresis
• Who was studied: Fresh human serum from a single donor, exposed in test tubes to monosodium urate monohydrate, potassium urate, calcium pyrophosphate dihydrate, hydroxyapatite, zymosan, asbestos, glass wool and eight microcrystalline steroid preparations; no people or animals were exposed
• Exposure: Asbestos described only as amphibole (no specific fiber type named), obtained from a laboratory supplier and weighed separately for each tube; listed in Table 1 at 14 mg/ml. The main material studied was monosodium urate monohydrate.
• Main results:
  • Asbestos, glass wool and the steroid crystals activated little or no C3
  • The asbestos and glass preparations showed little activity even when tested in larger doses
  • Monosodium urate monohydrate gave a mean excess converted area of 26.5%, the highest of all crystals tested
  • Only zymosan exceeded monosodium urate, with an excess of 43%
  • Calcium pyrophosphate dihydrate crystals gave an average difference of 11.5%
  • Potassium urate gave 9.0% and hydroxyapatite gave 5.3%, both significant
  • Of eight steroid preparations, only prednisolone acetate (Meticortelone) activated significantly more C3 than saline controls
  • Monosodium urate monohydrate activated C3 at the smallest amount tested, 0.2 mg/ml, within one hour
  • EGTA reduced C3 activation by monosodium urate monohydrate to the level seen in the control tube alone
  • Adding extra calcium or magnesium to serum that had not been treated with EDTA or EGTA inhibited C3 conversion
• The authors' conclusion: The author concluded that complement activation by monosodium urate monohydrate in whole serum is calcium dependent and occurs through the classic pathway. The author also reported that the degree of C3 activation paralleled the crystals' known inflammatory potential.
• Limitations the authors state:
  • Significant C3 activation occurred in control tubes, probably from contact between serum and the tube wall
  • The measured percent area does not directly equal the percent by weight of C3 actually activated
  • The dose chosen for comparing crystals tends to magnify the relative activity of less active crystals compared with monosodium urate monohydrate
  • C3 activation by the steroid crystals was at the limit of what the assay could detect
  • The author did not conclude that complement activation is the main reason these crystals cause inflammation

Topics

Medical terms in this study, explained in our Lexicon: Crystalline, Cation.

Related studies

• Binding of immunoglobulin and activation of complement by asbestos fibers — P. Hasselbacher (1979)
• Interactions of chrysotile asbestos fibres with the complement system — J.M. Saint-Remy, P. Cole (1980)
• Recent developments in immune activation by uric acid crystals — G. Ng, E.M. Chau, et al. (2010)
• Pulmonary macrophages are attracted to inhaled particles through complement activation — D.B. Warheit, L.H. Overby, et al. (1988)
• Mineral fiber-induced leukocyte activation: the role of intra- and extracellular calcium — M. Ruotsalainen, J. Naarala, et al. (1995)
• Differences between particulate and peptide stimuli on activation of oxidant production in alveolar macrophages — G.E. Hatch, A. Spock, et al. (1980)

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