The monocyte chemotactic protein-4 induces oxygen radical production, actin reorganization, and CD11b up-regulation via a pertussis toxin-sensitive G-protein in human eosinophils.
The novel human CC-chemokine monocyte chemotactic protein-4 (MCP-4) is a chemotaxin for eosinophils. Here, the biological activities and the activation profile of MCP-4 was further characterized in eosinophils and compared to other activators such as platelet activating factor (PAF), Eotaxin and RANTES. As demonstrated by lucigenin-dependent chemiluminescence and superoxide dismutase-inhibitable cytochrome C reduction MCP-4 stimulated the production of reactive oxygen metabolites. Furthermore, MCP-4 induced up-regulation of the integrin CD11b. Flow cytometric studies revealed rapid and transient actin polymerization upon stimulation with MCP-4. At optimal concentrations the changes induced by MCP-4 were weaker than the effects after stimulation with PAF and comparable to those obtained by RANTES and Eotaxin. Cell responses elicited by MCP-4 were inhibited by pertussis toxin indicating involvement of Gi-proteins in this signal pathway. These findings point to a role of MCP-4 in the pathogenesis of eosinophilic inflammation as chemotaxin as well as activator of pro-inflammatory effector functions.
Tenscher
K
K
Department of Dermatology, University of Freiburg, Germany.
Metzner
B
B
Hofmann
C
C
Schöpf
E
E
Norgauer
J
J
D000199:Actins / Q000097:blood*; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D008163:Luminescent Measurements; D016177:Macrophage-1 Antigen / Q000096:biosynthesis* / Q000097:blood; D018945:Monocyte Chemoattractant Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D037342:Pertussis Toxin; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013481:Superoxides / Q000097:blood; D015854:Up-Regulation / Q000187:drug effects*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D000199:Actins; C099677:CCL13 protein, human; D016177:Macrophage-1 Antigen; D018945:Monocyte Chemoattractant Proteins; D017382:Reactive Oxygen Species; D010566:Virulence Factors, Bordetella; D013481:Superoxides; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins