CHARACTERIZATION OF A CLASS OF NONFORMYLATED ENTEROCOCCUS-FAECALIS-DERIVED NEUTROPHIL CHEMOTACTIC PEPTIDES - THE SEX-PHEROMONES
CHARACTERIZATION OF A CLASS OF NONFORMYLATED ENTEROCOCCUS-FAECALIS-DERIVED NEUTROPHIL CHEMOTACTIC PEPTIDES - THE SEX-PHEROMONES
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DOI：
10.1073/pnas.87.1.66
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发表时间：
1990-01-01
影响因子：
11.1
通讯作者：
MARASCO, WA
中科院分区：
文献类型：
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作者：
SANNOMIYA, P;CRAIG, RA;MARASCO, WA
细菌在培养滤液中产生中性粒细胞趋化剂的异质混合物。甲酰甲硫氨酰肽已被证明在细菌培养物滤液中具有显着的趋化活性；然而，并非细菌培养物滤液中的所有趋化剂都是甲酰化肽。为了检验来自细菌的非甲酰化肽是否可以充当趋化剂，我们研究了几种来自粪肠球菌的非甲酰化七肽和八肽性信息素、它们的修饰衍生物以及它们用于激活大鼠腹膜中性粒细胞的竞争性抑制剂。其中一些肽，特别是 cAM373 和 cPD1，被证明是亚微摩尔浓度的有效趋化剂以及溶酶体颗粒酶分泌的诱导剂。此外，更具生物活性的肽能够与 fMet-Leu[3H]Phe 竞争与甲酰基肽受体的结合。这些研究证明，甲酰甲硫氨酰部分可能只是二肽和三肽与甲酰肽受体结合的绝对需要。可能具有或可能允许肽和受体之间额外的接触点的较大肽可能仅相对地需要N-甲酰化。事实上，通过消除这种结构限制，甲酰基肽受体可以与无限数量的感染源和宿主源的肽片段相互作用，然后调节中性粒细胞对感染和炎症的反应。
Bacteria produce a heterogeneous mixture of neutrophil chemotactic agents in culture filtrates. Formylmethionyl peptides have been shown to comprise a significant portion of the chemotactic activity in bacterial culture filtrates; however, not all of the chemotactic agents in bacterial culture filtrates are formylated peptides. To examine whether nonformylated peptides derived from bacteria could act as chemotactic agents, we studied several nonformylated hepta- and octapeptide Enterococcus faecalis-derived sex pheromones, their modified derivatives, and their competitive inhibitors for activation of rat peritoneal neutrophils. Several of these peptides, in particular cAM373 and cPD1, proved to be potent chemotactic agents in submicromolar concentrations as well as inducers of lysosomal granule enzyme secretion. Moreover, the more biologically active peptides were able to compete with fMet-Leu[3H]Phe for binding to the formyl peptide receptor. These studies demonstrate that the formylmethionyl moiety may be an absolute requirement only for the binding of di- and tripeptides to the formyl peptide receptor. Larger peptides that may have or that may allow for additional contact points between the peptide and receptor may require N-formylation only relatively. Indeed, by removing this structural restraint, the formyl peptide receptor may interact with an unlimited number of peptide fragments of both infectious and host origins to then modulate neutrophil responses to infection and inflammation.