Human recombinant i1istaminr releasing factor (hrhrf): a unique interleukin

We have recenlly suhcloncd fi gene and expressed a protein (IhllRF) Ihjil causes Igβ-dependent liistaminé release (flli) from n suhpupulatioii of allergic donors' basophils (Science 269: 688, 1995). llrllRP also stimulates IL-4 secretion from ba.sophils bearing lgF,+, Hie IgE molecule thai interacts witli JlrHRF (J. E. M. in press), and primes basophils from donors bearing IgE-, the IgE that does not interact with HrHRF, for HR and IL-4 secretion. Since affinity Chromatograph y and ELIS As failed to show direct binding of HrHRF to lgE+, we suggest that HrHRF interacts with its own receptor rallier than directly with IgE+. The present series of experiments were carried out to further explore the effects of HrHRF on basophils and to examine whether it also interacted with eosinophils. In the former experiments, we investigated whether HrHRF could prime basophils for IL-13 production. Cells prepared on Percoll gradients (5-25% basophils) were pretreated for 15 min with HrHRF (2 x 10 ~7M), then activated for 4 hours with 10 ng/ml of anli-IgE antibody. This priming with HrHRF enhanced IL-13 protein secretion by 36% above control. In the later experiments, eosinophils were purified on Percoll gradients and negative selection with magnetic beads to greater than 95% purity. Exposure of eosinophils to HrHRF for 30 min resulted in shedding of the adhesion molecule L-selectm, as assessed by FACS analysis, an effect usually seen with cytokines and chemotactrc factors, and in preliminary experiments, HrHRF caused chemotaxis of eosrnophils equal (o thai induced by the positive control, RANTHS. These data suggest thai llrHRF is a novel interleukin, which by interacting with its receptor, activates basophils and eosinophils, cells that are involved in allergic inflammatory processes.