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© The Rockefeller University Press, 0021-9525/1999//577 $5.00
The Journal of Cell Biology, Volume 147, Number 3, , 1999 577-588

Integrating Conflicting Chemotactic Signals

Ellen F. Foxman^a,b,c, Eric J. Kunkel^a,b,c, and Eugene C. Butcher^a,b,c

^a Laboratory of Immunology and Vascular Biology, Stanford University Medical School, Stanford, California 94305
^b Department of Pathology, Stanford University Medical School, Stanford, California 94305
^c Center for Molecular Biology and Medicine, Foothill Research Center, Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304
c/o Eugene C. Butcher, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305.(650) 858-3986(650) 852-3369

egf{at}leland.stanford.edu

Leukocytes navigate through complex chemoattractant arrays, and in so doing, they must migrate from one chemoattractant source to another. By evaluating directional persistence and chemotaxis during neutrophil migration under agarose, we show that cells migrating away from a local chemoattractant, against a gradient, display true chemotaxis to distant agonists, often behaving as if the local gradient were without effect. We describe two interrelated properties of migrating cells that allow this to occur. First, migrating leukocytes can integrate competing chemoattractant signals, responding as if to the vector sum of the orienting signals present. Second, migrating cells display memory of their recent environment: cells' perception of the relative strength of orienting signals is influenced by their history, so that cells prioritize newly arising or newly encountered attractants. We propose that this cellular memory, by promoting sequential chemotaxis to one attractant after another, is in fact responsible for the integration of competitive orienting signals over time, and allows combinations of chemoattractants to guide leukocytes in a step-by-step fashion to their destinations within tissues.

Key Words: leukocyte • neutrophil • chemokinesis • chemotaxis • cellular memory

© 1999 The Rockefeller University Press

Portions of this work are included, along with additional experiments, in Dr. Foxman's Ph.D. dissertation (Foxman 1999).

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