CELLULAR MEMORY - NEUTROPHIL ORIENTATION REVERSES DURING TEMPORALLY DECREASING CHEMOATTRACTANT CONCENTRATIONS

Cell directional orientation or shape polarization is the first cellul ar step in neutrophil locomotion. To better understand how chemoattrac tants interact with cells, we studied neutrophil polarization (or shap e changes) during exposure to a temporally decreasing chemoattractant signal of N-formyl-methionyl-leucyl-phenylalanine (FMLP) in the absenc e of a spatial concentration gradient. To accomplish this objective, w e used a manifold of differing FMLP concentrations attached to a stopp ed-flow microscope chamber. Spatial gradients of a fluorescent chemota ctic peptide could not be detected in the chamber by using microfluoro metry. When FMLP was injected at continually increasing concentrations at 10-s intervals, the shape and relative direction of the neutrophil persisted. However, when temporally decreasing FMLP concentrations we re injected, approximate to 80% of the cells changed their direction w ith 44% of the total cells swinging about to 180 degrees +/- 15 degree s, Most of these directional changes involved dissolution of both the lamellipodium and uropod and reformation of these structures 180 degre es from their original positions. This research suggests that neutroph ils reverse their morphological polarity when exposed to temporally de creasing ligand concentrations by ''remembering'' their ligand exposur e history and relative direction.