Defective leukocyte fungicidal activity in end-organ resistance to 1,25-dihydroxyvitamin d

A. Etzioni, Z. Hochberg, S. Pollak, T. Meshulam, V. Zakut, E. Tzehoval, Y. Keisari, I. Aviram, Z. Spirer, A. Benderly, Y. Weisman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Recent studies have shown l,25(OH)2D3 receptor-mediated modulation of leukocyte proliferation, differentiation, and function. We examined the phagocytosis and killing of microorganisms by neutrophils and monocytes from five patients of three families with hered­itary resistance to l,25(OH)2D3.Phagocytosis of microorganisms by patients’ neutrophils and monocytes was normal. However, defective neutrophil killing activity toward Candida albicans (30-40% of controls) was found in all patients. The killing of Staphylococcus aureus was normal. The neutrophil chemiluminescence, nitroblue tet-razolium (NBT) dye reduction, and the generation of superoxide ions and hydrogen peroxide by neutrophils and monocytes after induction by either soluble stimuli or zymozan particles, did not differ from those in controls. The neutrophil myeloperoxidase activity was also normal. Monocytes obtained from two patients of different families before long-term calcium infusion therapy and after they became normocalcemic, demonstrated a similar impaired fungicidal activity toward Saccharomyces cerevisiae, indicating that hypocalcemia itself was not the cause of the killing defect. However, the addition of the Ca+2 ionophore A23187 (1 µM) to the test medium restored the monocyte fungicidal activity to normal. As patients’ neutrophil cyto-solic free calcium concentration was similar to that in controls, it is suggested that l,25-(OH)2D3 exerts its effect on leukocyte function by a putative receptor-mediated regulation of subcellular calcium localization which may be important for fungicidal activity.

Original languageEnglish
Pages (from-to)276-279
Number of pages4
JournalPediatric Research
Issue number3
StatePublished - Mar 1989


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