RANTES AND RELATED CHEMOKINES ACTIVATE HUMAN BASOPHIL GRANULOCYTES THROUGH DIFFERENT G-PROTEIN-COUPLED RECEPTORS

被引:201
作者
BISCHOFF, SC
KRIEGER, M
BRUNNER, T
ROT, A
VONTSCHARNER, V
BAGGIOLINI, M
DAHINDEN, CA
机构
[1] UNIV HOSP BERN,INSELSPITAL,INST CLIN IMMUNOL,BERN,SWITZERLAND
[2] SANDOZ GMBH,VIENNA,AUSTRIA
[3] UNIV BERN,THEODOR KOCHER INST,CH-3001 BERN,SWITZERLAND
关键词
CHEMOKINES; RANTES; BASOPHILS; CHEMOTAXIS; LEUKOTRIENES;
D O I
10.1002/eji.1830230329
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-1alpha (MIP-1alpha) 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-1alpha elicited relatively weak chemotaxis and release responses, but was effective at considerably lower concentrations than MCP-1 and RANTES. MIP-1beta, by contrast, despite its high homology to MIP-1alpha, was totally inactive. Normodense human eosinophils, tested for comparison, responded in a similar fashion to RANTES and MIP-1alpha, but were unresponsive to MCP-1 and MIP-1beta. All CC-chemokines except MIP-1beta 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-1alpha.
引用
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页码:761 / 767
页数:7
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