COMPLEMENT PEPTIDE C3A INHIBITS IGE-MEDIATED TRIGGERING OF RAT MUCOSAL MAST-CELLS

The relationship between mast cells' secretory response to stimulation via their type 1 Fc epsilon receptors (Fc epsilon RI) and that provid ed by the C3a fragment of the complement system was investigated in th e rat mucosal-type mast cell line RBL-2H3. These cells are known to be unresponsive to the so-called 'peptidergic' stimulus provided by cati onic agents, such as anaphylatoxins, neuropeptides or polyamines, We n ow observed that C3a effectively inhibits the Fc epsilon RI clustering induced secretion of RBL-2H3 cells. This inhibition is dose-dependent and takes place at a C3a concentration range of 0.4-12.5 nM, i,e, at least three orders of magnitude lower than those where this anaphylato xin exerts its secretory stimulus to 'serosal' mast cells. In order to identify where C3a interferes in the Fc epsilon RI coupling cascade, we have studied its effect on the cells' protein phosphorylation patte rn, hydrolysis of phosphatidyl inositides, transient rise in free cyto solic Ca2+ ion concentration and Ca2+ uptake, All these processes were found to be inhibited by a similar C3a concentration range.