S100 PROTEIN CP-10 STIMULATES MYELOID CELL CHEMOTAXIS WITHOUT ACTIVATION

Leukocyte recruitment to inflammatory foci is generally associated wit h cellular activation. Recent evidence suggests that chemotactic agent s can be divided into two classes, ''classical chemoattractants'' such as FMLP, C5a, and IL-8, which stimulate directed migration and activa tion events and ''pure chemoattractants'' such as TGF-beta 1 which inf luence actin polymerisation and movement but not oxidative burst and a ssociated granular enzyme release. The studies reported here demonstra te that the murine S100 chemoattractant protein, CP-10, belongs to the ''non-classical'' group. Despite its potent chemotactic activity for neutrophils and monocytes/macrophages, CP-10 failed to increase [Ca2+] (i) in human or mouse PMN, although chemotaxis was inhibited by pertus sis toxin, confirming the suggestion of a novel Ca2+-independent G-pro tein-coupled pathway for postreceptor signal transduction triggered by ''pure chemoattractants.'' The co-ordinated up-regulation of Mac-1 an d down-regulation of L-selectin induced by FMLP on human PMN in vitro was not observed with CP-10. Quantitative changes in immediate (30 s) actin polymerisation occurred with FMLP and CP-10-treated human PMN. T he relative F-actin increases induced in WEHI 265 monocytoid cells by FMLP and CP-10 was optimal at 60 s and declined over 120 s. F-actin ch anges reflected the concentration and potencies of the agonists requir ed to provoke chemotaxis. After 90 min, CP-10 profoundly altered cell shape and increased both cell size and F-actin within pseudopodia. The se changes are typical of those mediating leukocyte deformability, and CP-10 may mediate leukocyte retention within microcapillaries and the reby contribute to the initiation of inflammation in vascular beds. (C ) 1996 Wiley-Liss, Inc.