INDUCTION OF AGGREGATION OF RAJI HUMAN B-LYMPHOBLASTIC CELLS BY VASOACTIVE-INTESTINAL-PEPTIDE

Subsets of neurons in the thymic cortex, Peyer's patches and lymphoid tissues of the respiratory system deliver vasoactive intestinal peptid e (VIP) at nanomolar concentrations. The possible effects of VIP on B- cell adhesiveness in these tissues were examined in studies of the hom otypic aggregation (HA) of human B-lymphoblastoid cells of the Raji li ne, which express a mean of 27,950 VIP receptors/cell with a mean K(d) of 0.8 nM. Mean HA, assessed microscopically, attained a maximum of 5 4% after 8 hr with 0.1 mug/ml of phorbol 12-myristate 13-acetate (PMA) (P<0.01) and 31% after 24 hr with 10(-8) M VIP (P<0.05), as contraste d with 13% and 20% at the respective times in medium alone, and both s timuli also increased the mean size of aggregates. The presence of the phosphodiesterase inhibitor Ro 20-1724 permitted 10(-9) M VIP, which had no effect alone, to raise the mean cyclic AMP content of Raji cell s by more than 10-fold and concurrently to elevate mean HA from 55% in medium alone at 48 hr to 70% and from 55% at 72 hr to 68% (P<0.05 for both). Monoclonal antibodies to lymphocyte function-associated (LFA-1 ) adhesive protein and to intercellular adherence molecule-1 (ICAM-1) suppressed significantly the HA of Raji cells induced by VIP and PMA. The effects of VIP on compartmental immunity in the lungs and intestin es thus may be mediated in part by increases in lymphocyte adhesivenes s, which could contribute to the regional accumulation of specifically immunocompetent cells.