Linnekin D, Bowles C A, Murano G, MacVittie T J
Armed Forces Radiobiology Research Institute, Department of Experimental Hematology, Bethesda, Maryland.
Inflammation. 1990 Dec;14(6):691-703. doi: 10.1007/BF00916372.
Formylated peptides are potent stimulants of polymorphonuclear neutrophilic leukocyte (PMN) migration from species such as humans and rabbits. Interestingly, PMNs from dogs, cats, pigs and cows have been reported as refractory to N-formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP) and generally are believed not to express formylpeptide receptors. Formylpeptides are a major component of conditioned media from E. coli cultures and believed to be a significant element in inflammatory responses elicited by E. coli. Our studies have found that E. coli filtrate was a potent stimulant of dog PMN migration. Inhibition of migration to E. coli filtrates by the antagonist t-botyloxycarbonyl-l-methionyl-l-leucyl-l-phenylalanine (t-boc-MLP) demonstrated that the migration was mediated through the formylated peptide receptor. Migration in response to peptides with higher affinity for the formylpeptide receptor than FMLP was further evidence for these receptors on the dog PMN. PMNs from dogs migrated in response to FMLP at high concentrations (100 microM); however, pretreatment with phorbol myristate acetate resulted in increased migration of dog PMNs in response to concentrations of FMLP as low as 1 pM. These results demonstrate that dog PMNs are responsive to formylpeptides and that these responses can be up-regulated by PMA. Thus PMNs from a species previously thought incapable of responding to formylpeptides can respond to formylpeptide analogs with high affinity for the receptor as well as be primed for enhanced migration to FMLP by PMA.
甲酰化肽是人类和兔子等物种中多形核嗜中性白细胞（PMN）迁移的有效刺激物。有趣的是，据报道狗、猫、猪和牛的PMN对N-甲酰-L-蛋氨酰-L-亮氨酰-L-苯丙氨酸（FMLP）不敏感，一般认为它们不表达甲酰肽受体。甲酰化肽是大肠杆菌培养条件培养基的主要成分，被认为是大肠杆菌引发炎症反应的重要因素。我们的研究发现，大肠杆菌滤液是狗PMN迁移的有效刺激物。拮抗剂叔丁氧羰基-L-蛋氨酰-L-亮氨酰-L-苯丙氨酸（t-boc-MLP）对大肠杆菌滤液迁移的抑制作用表明，这种迁移是通过甲酰化肽受体介导的。对甲酰肽受体亲和力高于FMLP的肽的迁移反应进一步证明了狗PMN上存在这些受体。狗的PMN在高浓度（100 microM）FMLP刺激下会发生迁移；然而，用佛波酯肉豆蔻酸酯预处理会导致狗PMN对低至1 pM浓度的FMLP的迁移增加。这些结果表明，狗的PMN对甲酰化肽有反应，并且这些反应可以被PMA上调。因此，以前认为无法对甲酰化肽作出反应的物种的PMN能够对与受体具有高亲和力的甲酰化肽类似物作出反应，并且可以通过PMA引发增强对FMLP的迁移。
