Monocyte chemotactic protein MCP-2 activates human basophil and eosinophil leukocytes similar to MCP-3.
It has been shown that CC chemokines activate basophil and eosinophil leukocytes with different selectivities and patterns of activity. The most effective are monocyte chemotactic protein-1 (MCP-1), a potent stimulus of mediator release in basophils without effects on eosinophils, RANTES, a weak stimulus of release and strong chemoattractant for basophils and eosinophils, and MCP-3, which combines the activities of MCP-1 and RANTES. We have now compared MCP-2, which has 62 and 60% of sequence identity with MCP-1 and MCP-3, respectively, with the other CC chemokines. MCP-2 induced mediator release by human basophils with lower efficacy and potency than MCP-1 and MCP-3. It promoted transient changes of cytosolic-free calcium concentration ([Ca2+]i) and chemotactic responses in both basophils and eosinophils, however somewhat less efficiently than MCP-3 and RANTES. Desensitization studies indicate that MCP-2 interacts with receptors recognizing MCP-1 as well as RANTES. These results demonstrate that MCP-2 and MCP-3 exert qualitatively similar biologic activities on basophils and eosinophils. In basophils that had not been treated with IL-3, MCP-2 induced minimal exocytosis only, but desensitized the cells toward MCP-1 and MCP-3, suggesting that MCP-2 may act as a functional inhibitor of CC chemokine actions. The results of this study further indicate that MCP analogues display partially distinct, partially overlapping bioactivities toward eosinophils and basophils, and may thus regulate inflammatory processes involving these effector cell types.
Weber
M
M
Institute of Immunology and Allergology, Inselspital, Bern, Switzerland.
Uguccioni
M
M
Ochensberger
B
B
Baggiolini
M
M
Clark-Lewis
I
I
Dahinden
C A
CA
D001491:Basophils / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054410:Chemokine CCL7; D054412:Chemokine CCL8; D002630:Chemotactic Factors / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects*; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007377:Interleukin-3 / Q000494:pharmacology; D017997:Leukotriene C4 / Q000378:metabolism; D008222:Lymphokines / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins; D018945:Monocyte Chemoattractant Proteins; D015846:Monokines / Q000494:pharmacology
C515450:CCL7 protein, human; C515453:CCL8 protein, human; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054410:Chemokine CCL7; D054412:Chemokine CCL8; D002630:Chemotactic Factors; D016207:Cytokines; D007377:Interleukin-3; D008222:Lymphokines; D019402:Macrophage Inflammatory Proteins; D018945:Monocyte Chemoattractant Proteins; D015846:Monokines; D017997:Leukotriene C4; D002118:Calcium