Sannomiya P, Craig R A, Clewell D B, Suzuki A, Fujino M, Till G O, Marasco W A
Instituto de Ciencas Biomédicas, Universidade de Sào Paulo, Brazil.
Proc Natl Acad Sci U S A. 1990 Jan;87(1):66-70. doi: 10.1073/pnas.87.1.66.
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.
细菌在培养滤液中产生嗜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滤液的趋化活性中占很大一部分；然而，细菌培养滤液中的并非所有趋化剂都是甲酰化肽。为了研究源自细菌的非甲酰化肽是否可以作为趋化剂，我们研究了几种源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对大鼠腹腔嗜中性粒细胞激活的竞争性抑制剂。这些肽中的几种，特别是cAM373和cPD1，在亚微摩尔浓度下被证明是有效的趋化剂，也是溶酶体颗粒酶分泌的诱导剂。此外，生物活性更强的肽能够与fMet-Leu-[3H]Phe竞争结合甲酰肽受体。这些研究表明，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必要条件。可能具有或可能允许肽与受体之间有额外接触点的较大肽可能只相对需要N-甲酰化。事实上，通过去除这种结构限制，甲酰肽受体可能会与来自感染源和宿主源的无限数量的肽片段相互作用，进而调节嗜中性粒细胞对感染和炎症的反应。
