Biologic activities of the beta-chemokine TCA3 on neutrophils and macrophages.
Previous in vivo and in vitro studies demonstrated that the murine beta-chemokine TCA3 is a chemoattractant for monocytes/macrophages and neutrophils. The ability of TCA3 to activate these cell populations is now evaluated. Treatment with 10 to 20 nM rTCA3 induced a respiratory burst with the production of superoxide and hydrogen peroxide in both casein-elicited and unstimulated neutrophil and macrophage populations. In addition, TCA3 treatment induced the production of reactive nitrogen intermediates, whereas stimulation with higher concentrations (100 nM) of TCA3 induced the exocytosis of lysozyme and elastase in the presence of cytochalasin B (7 micrograms/ml). Subnanomolar concentrations (100 pM) of TCA3 also caused integrin-mediated increases of adhesiveness to fibrinogen by neutrophils and macrophages. Increased adhesiveness is the most sensitive assay for TCA3 bioactivity. TCA3 treatment appears to involve signaling through a G-protein-linked receptor as Pertussis toxin abolished the TCA3-mediated increase of adhesiveness and the production of reactive nitrogen intermediates. The dose dependence of the TCA3-mediated activities indicate a coordinated inflammatory response mediated by varying concentrations of TCA3.
Devi
S
S
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Laning
J
J
Luo
Y
Y
Dorf
M E
ME
D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion / Q000187:drug effects; D015550:Cell Degranulation / Q000187:drug effects; D054402:Chemokine CCL1; D019742:Chemokines, CC; D006224:Cricetinae; D016207:Cytokines / Q000494:pharmacology*; D005260:Female; D016209:Interleukin-8 / Q000494:pharmacology; D019272:Leukocyte Elastase; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009113:Muramidase / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects*; D009573:Nitrites / Q000032:analysis; D010196:Pancreatic Elastase / Q000378:metabolism; D054401:Receptors, CCR8; D011994:Recombinant Proteins / Q000494:pharmacology; D016897:Respiratory Burst / Q000187:drug effects
C065971:CCL1 protein, human; C489319:Ccr8 protein, mouse; D054402:Chemokine CCL1; D019742:Chemokines, CC; D016207:Cytokines; D016209:Interleukin-8; D009573:Nitrites; D054401:Receptors, CCR8; D011994:Recombinant Proteins; D009113:Muramidase; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase