BIOLOGIC ACTIVITIES OF THE MURINE BETA-CHEMOKINE TCA3

The murine beta-chemokine TCA3 was purified to homogeneity. The biolog ic activities of the purified glycoprotein were evaluated in vivo and in vitro. Mice injected i.p. with 1- to 100-ng purified rTCA3 exhibite d a rapid influx of neutrophils and macrophages. Increased numbers of neutrophils and monocytes were observed in peripheral blood within 15 min and peaked at 45 min. After 45 min neutrophil and macrophage level s were increased in the peritoneal exudate with peak levels occurring at 2 h, followed by a subsequent decline by 24 h. Inflammatory respons es were induced in a dose-dependent fashion. The in vivo inflammatory responses were mirrored by the pattern of TCA3-induced chemotaxis in v itro. Neutrophils and macrophages responded to similar concentrations of TCA3 (3 X 10(-9) to 10(-8) M). Lymph node cells responded to other chemokines but did not migrate to TCA3. We also demonstrated that rTCA 3 stimulates a transient increase in cytoplasmic free calcium in monoc ytic cells through a PTX-sensitive pathway. Cross-desensitization stud ies indicate that TCA3 acts independently of other beta-chemokines (MI P-1 alpha and RANTES) and the alpha-chemokine IL-8. Furthermore, TCA3 does not induce a Ca2+ flux in cells transfected with cDNA for the C-C CKR-1 chemokine receptor, supporting the conclusion that there are di stinct receptors for TCA3.