CHRONIC MYELOGENOUS LEUKEMIA-DERIVED BASOPHILIC GRANULOCYTES EXPRESS A FUNCTIONAL ACTIVE RECEPTOR FOR THE ANAPHYLATOXIN C3A

The receptor for the inflammatory peptide C3a has scarcely been examined on human cells. This work demonstrates that human tumor-derived basophilic granulocytes express C3a receptors, and presents parts of the hitherto unknown C3a-signal transduction. When incubated with IL-3, these cells specifically liberated histamine on C3a stimulation. Independent from IL-3, 240000 +/- 100000 receptors per cell with a K(d) of 5.6 +/- 0.9 nm were determined. [Ca2+]i increased from 120 +/- 35 nm to 300 +/- 80 nM after a C3a challenge, as measured by digital imaging fluorescence microscopy, and rested at its basal level in the presence of C3a-desArg, the immediate catabolic product of C3a in vivo. This [Ca2+]i increase could be completely desensitized homologously by C3a as well as inhibited by up to 75% by pertussis toxin. Thus, tumor-derived basophils are suitable for cloning of the human C3a receptor.