Kitayama J, Carr M W, Roth S J, Buccola J, Springer T A
Center for Blood Research, Harvard Medical School, Department of Pathology, Boston, MA 02115, USA.
J Immunol. 1997 Mar 1;158(5):2340-9.
At inflammatory sites in vivo, leukocytes may confront multiple, competing chemoattractive signals. We found significant differences between eosinophils and neutrophils in transendothelial chemotaxis to a chemoattractant diffusing from the lower chamber, when a chemoattractant that binds to another receptor is present at uniform concentration. The transendothelial migration of eosinophils to FMLP, C5a, RANTES, or MCP-3 was totally inhibited by the presence of the homologous chemoattractant, and only RANTES and MCP-3 showed mutual inhibition. C5a and to a lesser extent FMLP chemokinetically stimulated migration to RANTES and MCP-3, without stimulating random migration. Results with neutrophils contrasted. The presence of FMLP not only abrogated neutrophil transmigration to FMLP but also strongly decreased chemotaxis to C5a, IL-8, and Gro-alpha. Similarly, C5a inhibited neutrophil chemotaxis to IL-8 and Gro-alpha. IL-8 almost totally abrogated chemotaxis to Gro-alpha, but Gro-alpha only moderately inhibited chemotaxis to IL-8. Neither IL-8 nor Gro-alpha significantly inhibited transmigration to FMLP or C5a. Actin polymerization in eosinophils and neutrophils was desensitized by the same combinations of chemoattractants that desensitized chemotaxis. We conclude that eosinophils have at least three noninterfering receptor-signal transduction pathways for chemotaxis and actin polymerization. In contrast, the signaling pathways for FMLP, C5a, and IL-8/Gro-alpha in neutrophils are heterologously cross-desensitized, with a hierarchy of resistance to competing signals of FMLP > C5a > IL-8 > Gro-alpha, in agreement with previous results in neutrophils on the Ca2+-mobilizing response. These results may have important implications for the behavior of these cell types in inflammatory sites.
在体内的炎症部位，白细胞可能会面临多种相互竞争的趋化信号。当一种与另一种受体结合的趋化剂以均匀浓度存在时，我们发现嗜酸性粒细胞和中性粒细胞在对从下腔室扩散而来的趋化剂的跨内皮趋化作用上存在显著差异。嗜酸性粒细胞向FMLP、C5a、RANTES或MCP-3的跨内皮迁移完全受到同源趋化剂的抑制，只有RANTES和MCP-3表现出相互抑制。C5a以及在较小程度上FMLP在趋化动力学上刺激了向RANTES和MCP-3的迁移，而没有刺激随机迁移。中性粒细胞的结果则相反。FMLP的存在不仅消除了中性粒细胞向FMLP的迁移，还强烈降低了对C5a、IL-8和Gro-α的趋化作用。同样，C5a抑制中性粒细胞对IL-8和Gro-α的趋化作用。IL-8几乎完全消除了对Gro-α的趋化作用，但Gro-α仅适度抑制对IL-8的趋化作用。IL-8和Gro-α均未显著抑制向FMLP或C5a的迁移。嗜酸性粒细胞和中性粒细胞中的肌动蛋白聚合通过使趋化作用脱敏的相同趋化剂组合而脱敏。我们得出结论，嗜酸性粒细胞至少有三条用于趋化和肌动蛋白聚合的非干扰性受体信号转导途径。相比之下，中性粒细胞中FMLP、C5a和IL-8/Gro-α的信号转导途径存在异源交叉脱敏，对竞争信号的抗性等级为FMLP > C5a > IL-8 > Gro-α，这与之前关于中性粒细胞钙动员反应的结果一致。这些结果可能对这些细胞类型在炎症部位的行为具有重要意义。
