Burg M, Martin U, Bock D, Rheinheimer C, Köhl J, Bautsch W, Klos A
Institute for Nephrology, Medical College of Hannover, Germany.
J Immunol. 1996 Dec 15;157(12):5574-81.
We have analyzed the induction of the receptor for the anaphylatoxic peptide C3a (C3aR) by the immunomodulator IFN-gamma, the phorbol ester PMA, and dibutyryl cAMP (Bt2cAMP) in comparison with the C5a receptor (C5aR, CD88). For U937 cells, IFN-gamma and Bt2cAMP up-regulated the C3aR to the same extent, whereas Bt2cAMP was 20-fold more effective in C5aR induction. PMA increased the expression of the C5aR, and acted synergistically with IFN-gamma. In contrast, PMA did not increase specific 125I-hC3a binding, and actually antagonized C3aR induction by IFN-gamma. Two related human cell lines of the myeloblastic/monocytic lineage, HL-60 and Mono Mac 6, showed inducibility of the C3aR similar to U937 cells. The two receptors showed subtle differences in signal transduction. Despite comparable numbers of both receptors, IFN-gamma potentiated activation of the C5aR but not the C3aR, as measured by an increase in free cytosolic Ca2+ upon ligand activation. Interestingly, Bt2cAMP-treatment led to a functional response to C3a in U937 cells. Such differences in receptor regulation and signaling might underlie the partly differing physiologic effects of C3a and C5a on, for example, chemotaxis, induction of oxidative burst, or immunoregulatory functions.
我们已分析免疫调节剂γ干扰素、佛波酯PMA和二丁酰环磷腺苷（Bt2cAMP）对过敏毒素肽C3a受体（C3aR）的诱导作用，并与C5a受体（C5aR，CD88）进行比较。对于U937细胞，γ干扰素和Bt2cAMP上调C3aR的程度相同，而Bt2cAMP诱导C5aR的效果要强20倍。PMA增加C5aR的表达，并与γ干扰素协同作用。相反，PMA并未增加特异性125I-hC3a结合，实际上还拮抗γ干扰素对C3aR的诱导作用。髓母细胞/单核细胞系的两种相关人类细胞系HL-60和Mono Mac 6，显示出与U937细胞类似的C3aR诱导性。这两种受体在信号转导方面存在细微差异。尽管两种受体数量相当，但通过配体激活后游离胞质Ca2+的增加来衡量，γ干扰素增强C5aR的激活，但不增强C3aR的激活。有趣的是，Bt2cAMP处理导致U937细胞对C3a产生功能性反应。受体调节和信号转导方面的这些差异，可能是C3a和C5a在例如趋化性、氧化爆发诱导或免疫调节功能等方面部分不同生理效应的基础。
