BIOLOGIC ACTIVITIES OF THE BETA-CHEMOKINE TCA3 ON NEUTROPHILS AND MACROPHAGES

Previous in vivo and in vitro studies demonstrated that the murine bet a-chemokine TCA3 is a chemoattractant for monocytes/macrophages and ne utrophils. The ability of TCA3 to activate these cell populations is n ow evaluated. Treatment with 10 to 20 nM rTCA3 induced a respiratory b urst with the production of superoxide and hydrogen peroxide in both c asein-elicited and unstimulated neutrophil and macrophage populations. In addition, TCA3 treatment induced the production of reactive nitrog en intermediates, whereas stimulation with higher concentrations (100 nM) of TCA3 induced the exocytosis of lysozyme and elastase in the pre sence of cytochalasin B (7 mu g/ml). Subnanomolar concentrations (100 pM) of TCA3 also caused integrin-mediated increases of adhesiveness to fibrinogen by neutrophils and macrophages. Increased adhesiveness is the mast sensitive assay for TCA3 bioactivity. TCA3 treatment appears to involve signaling through a G-protein-linked receptor as Pertussis toxin abolished the TCA3-mediated increase of adesiveness and the prod uction of reactive nitrgen intermediates. The dose dependence of the T CA3-mediated activities indicate a coordinated inflammatory response m ediated by varying concentrations of TCA3.