INTERLEUKIN-3 AND GRANULOCYTE MACROPHAGE-COLONY-STIMULATING FACTOR RENDER HUMAN BASOPHILS RESPONSIVE TO LOW CONCENTRATIONS OF COMPLEMENT COMPONENT-C3A

Complement component C3a is an anaphylatoxin known to induce plasma exudation and smooth muscle contraction in tissues. The effects on inflammatory effector leukocytes, however, are poorly defined and controversial, being at best weak and occurring at very high C3a concentrations. Here, we examined the effect of C3a upon mediator release from human basophils, with and without pretreatment with interleukin 3 (IL-3), a hematopoietic growth factor recently found to profoundly modify the basophil response to various cell agonists. In the absence of cytokines, C3a, even at a concentration of 1 μM, was ineffective or only weakly stimulatory for basophil mediator release. However, when basophils were pretreated with IL-3 at concentrations of only 0.01-1 unit/ml, they became responsive to C3a, releasing large amounts of histamine and also generating leukotrienes. Surprisingly, almost optimal effects occurred with even very low C3a concentrations (1 nM). Another hematopoietic growth factor, granulocyte/macrophage-colony-stimulating factor (GM-CSF), was also found to render basophils capable of responding to C3a, but the effect was weaker than that of IL-3. C3a-induced histamine release and leukotriene generation occurred rapidly in IL-3-primed cells, being complete after 0.5 and 2 min, respectively. The rapid and strong degranulation response, occurring at very low concentrations of C3a, suggests the presence of a high-affinity C3a receptor on basophils, which might be inducible by cytokines. Our results demonstrate that, depending on the presence of IL-3 or GM-CSF, C3a is a potent basophil activator, and such a phenomenon could be of relevance in various inflammatory processes, especially hypersensitivity reactions.