Neutrophil leucocyte chemotaxis is not induced by a spatial gradient of chemoattractant

Chemotaxis and directed locomotion of neutrophil leucocytes are generally thought to be determined by the directed response of the cell to stable, spatial gradients of chemoattractants. In most cases, however, cells are also exposed to characteristic temporal changes in the attractant concentration during the lifetime of the gradient, especially as it develops. We have attempted to test whether neutrophils can respond to a spatial gradient in which these temporal changes are essentially absent. Gradients of formyl-peptides were made across a narrow barrier of agarose gel that separated two fluid reservoirs, and the cells were observed cinematographically as they moved between gel and glass. In gradients predeveloped at low temperature, at which cell motion and responses to attractant were inhibited, neutrophils showed no tendency to accumulate up-gradient when warmed to 37 degrees C. Yet their speed and turning behaviour was related to the local concentration of formyl-peptide. However, gradients that developed at 37 degrees C, whilst the cells were responsive, elicited directed locomotion. We also tested populations that were either spreading into or already evenly distributed across micropore filters to see how cells might sense directional cues. We reasoned that evenly distributed populations could accumulate in a spatial gradient only if cells were able to 'read' it. However, no redistribution occurred without an applied impulse of attractant. It seems that the oriented, temporal component of an attractant signal is essential if a directed response (i.e. non-random turning) is to occur; a spatial gradient of soluble attractant alone does not induce neutrophil accumulation or taxis. This finding has implications for the termination of the acute inflammatory response, for clinical tests of leucocyte behaviour and for morphogen signal interpretation by cells in developing tissues.