Calreticulin is an interleukin-3-sensitive calcium-binding protein in human basophil leukocytes

Allergy. 2001 Jan;56(1):21-8. doi: 10.1034/j.1398-9995.2001.00115.x.


Background: IL-3 enhances basophil histamine release upon stimulation with any known secretagogue. The molecular mechanism behind this regulation is not known, although some observations suggest that IL-3 modulates the calcium part of the signal transduction mechanism. The inhibitory action of glucocorticoids on basophils can be reversed by stimulation with IL-3.

Methods: Calcium-binding proteins in the basophil cell line KU812 were identified by two-dimensional gel electrophoresis, Calcium-overlay assay, N-terminal sequence analysis, and mass spectometry. The presence of the same proteins in purified human basophil leukocytes was established by comigration of KU812 and human basophil proteins on the two-dimensional gels. The expression of the calcium-binding proteins in the absence and presence of IL-3 and/or anti-IgE was determined by densitometric measurement of the spots on the two-dimensional gels.

Results: Calreticulin was identified on the two-dimensional gel of KU812 proteins. A protein with exactly the same migration pattern was found on the gels of proteins from purified human basophils. Immunoblotting with a specific antihuman calreticulin antibody confirmed that this protein was calreticulin. Subsequent analysis showed that the expression of calreticulin in the basophils is upregulated twofold upon stimulation with rhIL-3, even in doses below those needed for enhancement of histamine release.

Conclusions: The expression of calreticulin in human basophil leukocytes is regulated by IL-3. Calreticulin is known to modulate IP3-dependent Ca2+ influx in different cell systems, and calreticulin overexpression inhibits steroid-induced transcriptional activation. Therefore, modulation of calreticulin expression may be one mechanism by which IL-3 exerts its effects on human basophils.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basophils / drug effects
  • Basophils / metabolism*
  • Calcium / metabolism
  • Calcium-Binding Proteins / metabolism*
  • Calreticulin
  • Cell Line
  • Dose-Response Relationship, Drug
  • Electrophoresis, Gel, Two-Dimensional
  • Gene Expression
  • Humans
  • Interleukin-3 / pharmacology*
  • Ribonucleoproteins / metabolism*


  • Calcium-Binding Proteins
  • Calreticulin
  • Interleukin-3
  • Ribonucleoproteins
  • Calcium