Ca2+ and IgE

Two decades ago, 10% calcium gluconate had been recommended for the treatment of anaphylaxis (couldn’t find any explanation for that but renember one of my teachers saying it will stabilize the membranes). There is now an update in scienceblog:doi:10.1038/ni1441: Mice lacking the calcium-activated nonselective cation channel TRPM4 (trmp4-/-) loose the ability to suppress Ca2+ influx in mast cells that otherwise leeds to degranulation and histamine release.

BTW – I am always wondering about the dual function of vitamin D on calcium homeostasis and immune regulation. Sure, bones simply are a large Ca2+ reservoir and the large-conductance Ca2+-activated K+ channel is essential for innate immunology (scienceblog:doi:10.1038/nature02356) but the TRPM4 story is probably the best example linking both systems besides vitamin D.

Addendum 15/9/08

An update on STIM1

Allergen stimulation induces Ca2+ influx and elicits the secretion of inflammatory mediators from mast cells. Here we show … that cells lacking [the Ca2+-binding endoplasmic reticulum protein] STIM1 had much less degranulation and cytokine production after Fcepsilon RI stimulation.

and CRACM1

CRACM1 (also called Orai1) constitutes the pore subunit of store-operated calcium release–activated calcium channels … Mast cells derived from CRACM1-deficient mice showed grossly defective degranulation and cytokine secretion, and the allergic reactions elicited in vivo were inhibited … CRACM1 is crucial in mouse mast cell effector function.

plus two papers, one on blunted IgE-mediated activation of mast cells in mice lacking a Ca2+ channel and another one on elevated calcium activating IL4 transcription.

Addendum 27/11/09

Finally, I had the chance to hear Stefan yesterday in Großhadern on Orai1 – a truely excellent talk. Orai1 defective knock in mice seem to have an abrogated (his slide said attenuated) delayed hypersensitivity as found in the ear swelling test.

Addendum 18/6/10

Thanks to SD, here is an old JACI paper that confirms my clinical experience of an immediate Ca2+ effect on symptom relief: