Basophil variants with impaired cromoglycate binding do not respond to an immunological degranulation stimulus

Cromoglycate, which inhibits IgE-mediated degranulation of mast cells ^1,2 and a basophilic rat tumour cell line (RBL-2H3) (ref. 3), is a drug widely used in the treatment of allergic asthma. We have demonstrated the presence of specific binding sites for that drug on the membranes of basophils and mast cells⁴ and more recently, we have succeeded in isolating the cromoglycate-binding protein from the membranes of RBL-2H3 cells⁵. These findings together with the chelation by cromoglycate of alkaline-earth ions in low polarity medium^6,7, suggest that the binding site of the drug may either be part, or closely related to the calcium gate. To further investigate this, we have selected variants of the RBL-2H3 cell line that are defective in cromoglycate binding but bind IgE normally. In these variants, which have similar histamine content to the parental cells, IgE-mediated challenge did not lead to Ca²⁺ influx, degranulation and histamine release. In contrast, these cells were able to release histamine on exposure to the Ca²⁺ ionophore A23187, indicating that the degranulation mechanism distal to the Ca²⁺ gating step is unaffected. Taken together, these findings suggest that cromoglycate-binding protein has a role in the transmem-brane calcium influx which induces degranulation.