RANTES and related chemokines activate human basophil granulocytes through different G protein-coupled receptors.
Chemotactic cytokines related to interleukin-8 (IL-8; CXC-chemokines) or monocyte chemotactic protein-1 (MCP-1; CC-chemokines) have been shown to stimulate human basophils, and are considered important tissue-derived mediators of inflammation. We have studied the effects of four CC-chemokines and show that MCP-1, RANTES (regulated on activation, normal T expressed and secreted) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) are potent basophil agonists inducing a rapid change of cytosolic free calcium ([Ca2+]i), the release of histamine and sulfido-leukotrienes, and chemotaxis. MCP-1 was the most potent stimulus of release, and the only chemokine that induced marked exocytosis in basophils without pretreatment with interleukin-3. RANTES was the strongest stimulus of chemotaxis, but only a moderate stimulus of release. MIP-1 alpha elicited relatively weak chemotaxis and release responses, but was effective at considerably lower concentrations than MCP-1 and RANTES. MIP-1 beta, by contrast, despite its high homology to MIP-1 alpha, was totally inactive. Normodense human eosinophils, tested for comparison, responded in a similar fashion to RANTES and MIP-1 alpha, but were unresponsive to MCP-1 and MIP-1 beta. All CC-chemokines except MIP-1 beta induced a similar rapid and transient rise of [Ca2+]i that was sensitive to pertussis toxin, indicating that they activate basophils via G-protein-coupled receptors. Cross-desensensitization experiments indicate that basophils bear different CC-chemokine receptors. Some interact selectively with MCP-1 or RANTES, while others are shared by RANTES and MIP-1 alpha.
Bischoff
S C
SC
Institute of Clinical Immunology, Inselspital, Bern.
Krieger
M
M
Brunner
T
T
Rot
A
A
von Tscharner
V
V
Baggiolini
M
M
Dahinden
C A
CA
D001491:Basophils / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D002630:Chemotactic Factors / Q000502:physiology; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000502:physiology; D004804:Eosinophils / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology*; D006636:Histamine Release; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000502:physiology; D015289:Leukotrienes / Q000096:biosynthesis; D008222:Lymphokines / Q000502:physiology*; D019402:Macrophage Inflammatory Proteins; D009000:Monocytes / Q000502:physiology; D015846:Monokines / Q000502:physiology; D037342:Pertussis Toxin; D011956:Receptors, Cell Surface / Q000502:physiology*; D011994:Recombinant Proteins; D015398:Signal Transduction; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D002630:Chemotactic Factors; D016207:Cytokines; D016209:Interleukin-8; D015289:Leukotrienes; D008222:Lymphokines; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D002118:Calcium