Leukocyte recruitment to inflammatory foci is generally associated with cellular activation. Recent evidence suggests that chemotactic agents can be divided into two classes, "classical
chemoattractants" such as FMLP, C5a, and
IL-8, which stimulate directed migration and activation events and "pure
chemoattractants" such as
TGF-beta 1 which influence actin polymerisation and movement but not oxidative burst and associated granular
enzyme release. The studies reported here demonstrate 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
pertussis toxin, confirming the suggestion of a novel Ca(2+)-independent
G-protein-coupled pathway for post-receptor signal transduction triggered by "pure
chemoattractants." The co-ordinated up-regulation of Mac-1 and 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. The 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 changes reflected the concentration and potencies of the agonists required to provoke chemotaxis. After 90 min,
CP-10 profoundly altered cell shape and increased both cell size and
F-actin within pseudopodia. These changes are typical of those mediating leukocyte deformability, and
CP-10 may mediate leukocyte retention within microcapillaries and thereby contribute to the initiation of
inflammation in vascular beds.