DIFFERENTIAL RESPONSE OF HUMAN BASOPHILS AND MAST-CELLS TO RECOMBINANT CHEMOKINES

Chemokines are proinflammatory peptides regulating the functions of va rious hematopoietic cells. We have analyzed the effects of seven recom binant human (rh) chemokines (MCAF, RANTES, MIP-1 alpha, MIP-1 beta, I L-8, GRO, and IP-10) on the growth and function of human basophils and mast cells. We found that MCAF, but not RANTES, MIP-1 alpha, MIP-1 be ta, IL-8, GRO, or IP-10, causes direct and dose-dependent histamine re lease from basophils (MCAF, 5 mu g/ml: 26.9 +/- 3.4%; other chemokines : < 5% of total histamine). An increased (2.1 to 3.5-fold) response to MCAF was obtained when basophils were preincubated with rh interleuki n-3 (100 units/ml). Moreover, IL-3-primed basophils became responsive to physiologic concentrations (< 1 mu g/ml) of MCAF, IL-8, and RANTES. None of the chemokines tested was able to induce histamine secretion in mast cells obtained from lung (n = 2), skin (n = 1), uterus (n = 3) , or tonsils (n = 3), even when cells had been preincubated with the m ast cell agonist SCF. The chemokines also failed to modulate the expre ssion of activation antigens (CD11b/C3biR, CD25/IL-2R beta, CD63, IL-3 R alpha, CD117/c-kit) on the mast cell line HMC-1 or the basophil cell line KU-812 and were unable to induce differentiation of basophils or mast cells in culture. Together, our results show that basophils resp ond to rhIL-8, rhMCAF, and rhRANTES and that, unlike human basophils, human mast cells are unresponsive to recombinant chemokines.