No abstract

Movement towards or away from a given stimulus guides the directional migration of prokaryotes, simple eukaryotes and neurons. As bi-directional cues may influence entry and exit of immune effector cells from tissue sites, we evaluated the migratory responses of T-cell subsets to varying concentrations of the chemokine stromal cell derived factor-1 (SDF-1). There was selective repulsion of subpopulations of T cells at high concentrations of recombinant SDF-1 or naturally occurring bone marrow-derived SDF-1, which could be inhibited by pertussis toxin and antibody against the chemokine receptor CXCR4. Distinct sensitivity profiles to genistein, herbimycin and 8-Br-cAMP biochemically distinguished movement of cells towards or away from an SDF-1 gradient. In vivo, antigen-induced T-cell recruitment into the peritoneal cavity was reversed by high but not low concentrations of SDF-1. The phenomenon of movement away from a chemokine represents a previously unknown mechanism regulating the localization of mature T cells. It adds to the functional repertoire of chemokines that may participate in immune physiology and may be applied therapeutically to alter the immune response.

1 The depressant actions on evoked electrical activity and the excitant amino acid antagonist properties of a range of w-phosphonic x-carboxylic amino acids have been investigated in the isolated spinal cord preparations of the frog or immature rat. 2 When tested on dorsal root-evoked ventral root potentials, members of the homologous series from 2-amino-5-phosphonovaleric acid to 2-amino-8-phosphonooctanoic acid showed depressant actions which correlated with the ability of the substances to antagonize selectively motoneuronal depolarizations induced by N-methyl-D-aspartate. of this substance had a relatively weak and non-selective antagonist action on depolarizations induced by N-methyl-D-aspartate, quisqualate and kainate and a similarly weak depressant effect when tested on evoked electrical activity. The (+)-form was more potent than the (-)-form in depressing electrically evoked activity but did not antagonize responses to amino acid excitants. At concentrations higher than those required to depress electrically evoked activity, the (+)-form produced depolarization. This action was blocked by 2-amino-5-phosphonovalerate.

1 Dorsal roots (L3-L7) isolated from immature (1-9 day old) rats were depolarized selectively by kainate (I-1I00 M). L-Glutamate (25-1000 pM), but not L-aspartate, mimicked the action of kainate. N-methylaspartate had no activity on these preparations and quisqualate was thirty times less active than kainate.2 Depolarizations evoked by L-glutamate (100-1OO0pM) faded rapidly in the presence of Lglutamate. Depolarizations evoked by kainate were depressed during the fade induced by L-glutamate. 3 Certain electrically evoked C-fibre volleys in dorsal roots or leg nerves of rats at any age were selectively depressed or abolished in the presence of kainate. The effect of kainate was more selective than that of y-aminobutyric acid or capsaicin.