Leonard E J, Yoshimura T, Rot A, Noer K, Walz A, Baggiolini M, Walz D A, Goetzl E J, Castor C W
Immunopathology Section, National Cancer Institute, Frederick, Maryland 21701.
J Leukoc Biol. 1991 Mar;49(3):258-65. doi: 10.1002/jlb.49.3.258.
Neutrophil attractant/activation protein-1 (NAP-1) has sequence similarity to platelet factor-4 (PF-4) and to NAP-2 (a truncated from of connective tissue activating protein-III [CTAP-III(des 1-15)]. We compared chemotactic activity for neutrophils of these related proteins. We also included for comparison CTAP-III, CTAP-III(des 1-13), the C-terminal dodecapeptide of PF-4 [PF-4(59-70)], and C5a. Chemotactic potency (EC50) was highest for NAP-1 and C5a. Although chemotactic efficacy (peak percentage of neutrophils migrating) was comparable for C5a, NAP-1, and NAP-2, the NAP-2 response occurred only at concentrations 100-fold higher than the NAP-1 EC50 of 10(8) M. Data for the CTAP-III proteins confirmed that CTAP-III is not an attractant and that chemotactic activity appears as a result of cleavage of residues at the N-terminus to make CTAP-III(des 1-13) or NAP-2 [CTAP-III(des 1-15)]. Chemotactic activity of PF-4 was low and variable, with no significant response by neutrophils from six of nine subjects. In contrast, PF-4(59-70) regularly induced high chemotactic responses, although the EC50 of 1.6 x 10(5)M was 1,000-fold greater than that of NAP-1. The binding of fluoresceinated NAP-1 to neutrophils was inhibited by unlabeled NAP-1 or NAP-2 but not by PF-4 or PF-4 (59-70). This suggests that NAP-2 interacts with the neutrophil NAP-1 receptor. Despite the low chemotactic potency of NAP-2, it is a potential attractant at sites of injury because of the relatively large amounts of the parent CTAP-III released from platelets, as indicated by a serum concentration of approximately 10(-6) M.
中性粒细胞趋化因子/激活蛋白-1（NAP-1）与血小板因子-4（PF-4）以及NAP-2（结缔组织激活蛋白-III [CTAP-III（缺失1-15）]的截短形式）具有序列相似性。我们比较了这些相关蛋白对中性粒细胞的趋化活性。我们还纳入了CTAP-III、CTAP-III（缺失1-13）、PF-4的C末端十二肽[PF-4（59-70）]以及C5a用于比较。趋化效力（EC50）在NAP-1和C5a中最高。尽管C5a、NAP-1和NAP-2的趋化功效（迁移的中性粒细胞的峰值百分比）相当，但NAP-2的反应仅在浓度比NAP-1的EC50（10^8 M）高100倍时才出现。CTAP-III蛋白的数据证实CTAP-III不是一种趋化因子，趋化活性是由于N末端残基的切割产生CTAP-III（缺失1-13）或NAP-2 [CTAP-III（缺失1-15）]而出现的。PF-4的趋化活性较低且变化不定，9名受试者中有6名受试者的中性粒细胞没有明显反应。相比之下，PF-4（59-70）经常诱导出高趋化反应，尽管其1.6×10^5 M的EC50比NAP-1的EC50大1000倍。荧光素标记的NAP-1与中性粒细胞的结合被未标记的NAP-1或NAP-2抑制，但不被PF-4或PF-4（59-70）抑制。这表明NAP-2与中性粒细胞NAP-1受体相互作用。尽管NAP-2的趋化效力较低，但由于血小板释放的母体CTAP-III量相对较大，血清浓度约为10^-6 M，它在损伤部位是一种潜在的趋化因子。
