Detmers P A, Powell D E, Walz A, Clark-Lewis I, Baggiolini M, Cohn Z A
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY 10021.
J Immunol. 1991 Dec 15;147(12):4211-7.
Several structural homologues of the chemotactic peptide neutrophil-activating peptide 1/IL-8 (NAP-1/IL-8) were tested for their ability to influence the expression and function of adhesion-promoting receptors on human polymorphonuclear leukocytes (PMN). NAP-2, melanoma growth stimulatory activity, and two forms of NAP-1/IL-8 (ser-NAP-1/IL-8 and ala-NAP-1/IL-8, consisting of 72 and 77 amino acids, respectively), each caused an increase in the expression of CD11b/CD18 (CR3) and CR1, which was accompanied by a decrease in the expression of leukocyte adhesion molecule-1 (LAM-1, LECAM-1). The binding activity of CD11b/CD18 was also enhanced 3- to 10-fold by these peptides, but enhanced function was transient: binding of erythrocytes coated with C3bi reached a maximum by 30 min and declined thereafter. Ser-NAP-1/IL-8, ala-NAP-1/IL-8, NAP-2, and melanoma growth stimulatory activity also caused a two- to threefold enhancement of the phagocytosis of IgG-coated erythrocytes (EIgG) by PMN without causing a large increase in the expression of Fc gamma receptors. Enhanced phagocytosis of EIgG appeared to be mediated through CD11b/CD18, because F(ab')2 fragments of an antibody directed against CD18 inhibited NAP-1/IL-8-stimulated ingestion of EIgG. The four active peptides caused a rapid, transient increase in the amount of F-actin within PMN, indicating that they are capable of influencing the structure of the microfilamentous cytoskeleton, which participates in phagocytosis. Two other NAP-1/IL-8-related peptides, platelet factor 4 and connective tissue-activating peptide III, were without effect on expression of CD11b/CD18, CR1, and LAM-1, binding activity of CD11b/CD18, or Fc-mediated phagocytosis, and increased actin polymerization only slightly. Our observations indicate that several members of the NAP-1/IL-8 family of peptides were capable of promoting integrin-mediated adhesion and Fc-mediated phagocytosis, processes important in the recruitment of PMN to sites of inflammation and antimicrobial responses of PMN.
对趋化肽中性粒细胞激活肽1/白细胞介素-8（NAP-1/IL-8）的几种结构同源物进行了测试，以考察它们影响人多形核白细胞（PMN）上促进黏附受体的表达和功能的能力。NAP-2、黑素瘤生长刺激活性因子以及两种形式的NAP-1/IL-8（分别由72和77个氨基酸组成的丝氨酸-NAP-1/IL-8和丙氨酸-NAP-1/IL-8），每一种都能使CD11b/CD18（CR3）和CR1的表达增加，同时伴随着白细胞黏附分子-1（LAM-1，LECAM-1）表达的降低。这些肽还能使CD11b/CD18的结合活性增强3至10倍，但增强的功能是短暂的：包被有C3bi的红细胞的结合在30分钟时达到最大值，此后下降。丝氨酸-NAP-1/IL-8、丙氨酸-NAP-1/IL-8、NAP-2和黑素瘤生长刺激活性因子还能使PMN对IgG包被的红细胞（EIgG）的吞噬作用增强2至3倍，而不会使Fcγ受体的表达大幅增加。EIgG吞噬作用的增强似乎是通过CD11b/CD18介导的，因为针对CD18的抗体的F(ab')2片段可抑制NAP-1/IL-8刺激的EIgG摄取。这四种活性肽能使PMN内F-肌动蛋白的量迅速、短暂增加，表明它们能够影响参与吞噬作用的微丝细胞骨架的结构。另外两种与NAP-1/IL-8相关的肽，血小板因子4和结缔组织激活肽III，对CD11b/CD18、CR1和LAM-1的表达、CD11b/CD18的结合活性或Fc介导的吞噬作用均无影响，且仅略微增加肌动蛋白聚合。我们的观察结果表明，NAP-1/IL-8肽家族的几个成员能够促进整合素介导的黏附和Fc介导的吞噬作用，这些过程在PMN募集到炎症部位以及PMN的抗菌反应中很重要。
