Effect of structural modification at carbon atom 1 of leukotriene B4 on the chemotactic and metabolic response of human neutrophils.
Effect of structural modification at carbon atom 1 of leukotriene B4 on the chemotactic and metabolic response of human neutrophils.
复制标题
白三烯 B4 碳原子 1 的结构修饰对人中性粒细胞趋化和代谢反应的影响。
DOI：
10.1016/0003-2697(87)90488-x
复制
发表时间：
1987
影响因子：
2.9
通讯作者：
Hugli,TE
中科院分区：
文献类型：
--
作者：
Clancy,RM;Dahinden,CA;Hugli,TE
Human neutrophils biosynthesize the chemoattractant leukotriene B4(LTB4) and metabolize LTB4to omega oxidative products 20-hydroxy-LTB4(20-OH-LTB4) and 20-carboxy-LTB4(20-COOH-LTB4). In this study, we prepared the C-1 methyl ester and N-methyl amide of LTB4and then examined neutrophil chemotaxis and metabolism of these derivatives of LTB4. The results show that chemical modification of LTB4at carbon atom 1 dramatically affects metabolism of the lipid molecule. The free acid form of LTB4was taken up and metabolized by human neutrophils, while the methyl ester and N-methyl amide derivatives were poor substrates for omega oxidation. Although human neutrophils were poorly attracted to the methyl ester of LTB4, the amide derivative was a complete agonist of the neutrophil chemotactic response and displayed an ED50for chemotaxis identical to that of LTB4. Therefore, we concluded that omega oxidation is not a requirement for the neutrophil chemotactic response induced by LTB4. These results also indicate that the N-methyl amide of LTB4may be a useful ligand for the elucidation of molecular mechanisms operative in neutrophil chemotaxis to LTB4, since the C-1 derivative is not further metabolized. Two separate responses of human neutrophils are elicited by LTB4, resulting in both cellular activation and generation of omega oxidation products. It appears that putative receptors on the neutrophils can distinguish between LTB4and certain derivatives that are structurally identical except for modification at the C-1 position (i.e., the methyl ester). LTB4derivatives modified at the C-1 position do not undergo conversion to omega oxidation products by the neutrophil.
