S100 protein CP-10 stimulates myeloid cell chemotaxis without activation.
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.
Cornish
C J
CJ
Immunology Group, Heart Research Institute, Camperdown, New South Wales, Australia.
Devery
J M
JM
Poronnik
P
P
Lackmann
M
M
Cook
D I
DI
Geczy
C L
CL
D000199:Actins / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000494:pharmacology*; D040501:Calgranulin A; D002460:Cell Line; D002630:Chemotactic Factors / Q000494:pharmacology*; D015936:Complement C5a / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D019041:L-Selectin / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D009418:S100 Proteins
D000199:Actins; D002135:Calcium-Binding Proteins; D040501:Calgranulin A; D002630:Chemotactic Factors; D016177:Macrophage-1 Antigen; D009418:S100 Proteins; C086145:S100a8 protein, mouse; D019041:L-Selectin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D019204:GTP-Binding Proteins; D002118:Calcium