DISPERSIVE LOCOMOTION OF HUMAN NEUTROPHILS IN RESPONSE TO A STEROID-INDUCED FACTOR FROM MONOCYTES

A monocyte-derived factor that stimulates the locomotion of human neut rophils on an albumin-coated glass surface has been prepared from the culture supernatant of dexamethasone-treated human monocytes and calle d STMS (steroid-treated monocyte supernatant). A modified cell trackin g program has been developed and the parameters of locomotion determin ed by the analysis of Gall and Boone for cells moving in a persistent random walk. Cells moving in uniform concentrations of STMS, interleuk in-8 (IL-8) and N-formyl-methionyl-leucyl-phenylalanine (fMLP) chosen to give a sub-maximal speed of locomotion show persistent, random and constrained random diffusion, respectively, with augmented diffusion c oefficients of 0.8+/-0.1, 0.14+/-0.02 and 0.12+/-0.03 mu m(2) per seco nd for STMS, IL-8 and fMLP, respectively. The augmented diffusion coef ficient and the underlying persistence are therefore sensitive quantit ative assay parameters for STMS activity and the qualitative character istics of locomotion allow STMS activity to be distinguished from that of all other factors tested. The contribution of lowered adhesion to locomotion was examined in a novel tilt-assay, which demonstrated that cells in the presence of STMS, but not other factors, moved down slop e with significantly increased speed while maintaining contact with th e substratum. The results were interpreted in terms of the bipolar for m of STMS-treated cells, contrasting with multipolar forms in response to other agents. This together with low adhesiveness plus an inherent tendency of a single locomotor focus to continue motion in its origin al direction has been used to explain the difference between response to STMS and other factors. STMS has been proposed either to prevent di rected locomotion of neutrophils to an inflammatory site or to promote dispersive locomotion away from such a site and perhaps to inhibit ne utrophil transmigration between endothelial cells.