Kuna P, Reddigari S R, Schall T J, Rucinski D, Viksman M Y, Kaplan A P
Department of Medicine, State University of New York, Stony Brook 11794-8161.
J Immunol. 1992 Jul 15;149(2):636-42.
Chemotaxis of different populations of cells and release of proinflammatory mediators in response to antigenic stimulation are important processes in allergic diseases. These lead to the late phase response, a hallmark of chronic allergic diseases. Recombinant RANTES, a member of the "intercrine/chemokine" family of cytokines, has been previously shown to be chemotactic for monocytes and T cells of memory/helper phenotype. In this manuscript, we show that it is capable of inducing histamine release from human basophils at concentrations as low as 10(-10) M and compare its activity with that of monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 (MCAF/MCP-1), another intercrine/chemokine. RANTES (10(-7) M) caused histamine release from the leukocytes of 26 of 33 donors tested (mean 21.8 +/- 3.1%). In the same group of donors, MCAF/MCP-1, goat anti-human IgE (anti-IgE; 1 microgram/ml), and FMLP (10(-5) M) released 41.1 +/- 2.9%, 40.5 +/- 4.6%, and 44 +/- 3.1% histamine, respectively. The percent histamine release by RANTES in atopic vs nonatopics was 30.3 +/- 6.7 and 16.5 +/- 2.4, respectively (p less than 0.05), and histamine release by RANTES correlated significantly with histamine release by MCAF (r = 0.69; p less than 0.001) but not with histamine release by anti-IgE (r = 0.29; p greater than 0.05). Histamine release by RANTES and MCAF/MCP-1 was extremely rapid, reaching a maximum within 1 min. RANTES was also shown to activate highly purified basophils (80% pure), and its activity was inhibited by a polyclonal anti-RANTES antibody. At a suboptimal concentration (6 x 10(-9) M), RANTES did not prime basophils to enhance histamine release by secretagogues such as anti-IgE, C5a, or FMLP. On the other hand, preincubation of basophils with RANTES or MCAF/MCP-1 desensitized basophils to either factor but not to anti-IgE, C5a, or FMLP. Preincubation of basophils with pertussis toxin markedly diminished the basophil response to either RANTES or MCAF/MCP-1. These results suggest that RANTES and MCAF/MCP-1: 1) are potent activators of basophils; 2) may function via the same, or a closely related, receptor system in basophils; and 3) may represent a link between activation of monocytes, lymphocytes, and basophils in inflammatory disorders such as the late phase allergic reaction.
不同细胞群体的趋化作用以及对抗原刺激产生的促炎介质释放是过敏性疾病中的重要过程。这些过程会引发迟发相反应，这是慢性过敏性疾病的一个标志。重组RANTES是细胞因子“白细胞介素/趋化因子”家族的成员，先前已证明它对记忆/辅助表型的单核细胞和T细胞具有趋化作用。在本论文中，我们表明它能够在低至10^(-10) M的浓度下诱导人嗜碱性粒细胞释放组胺，并将其活性与另一种白细胞介素/趋化因子单核细胞趋化和激活因子/单核细胞趋化蛋白-1（MCAF/MCP-1）的活性进行比较。RANTES（10^(-7) M）导致33名受试供体中26名的白细胞释放组胺（平均21.8±3.1%）。在同一组供体中，MCAF/MCP-1、山羊抗人IgE（抗IgE；1微克/毫升）和FMLP（10^(-5) M）分别释放41.1±2.9%、40.5±4.6%和44±3.1%的组胺。特应性个体与非特应性个体中RANTES诱导的组胺释放百分比分别为30.3±6.7和16.5±2.4（p<0.05），且RANTES诱导的组胺释放与MCAF诱导的组胺释放显著相关（r = 0.69；p<0.001），但与抗IgE诱导的组胺释放不相关（r = 0.29；p>0.05）。RANTES和MCAF/MCP-1诱导的组胺释放极其迅速，在1分钟内达到最大值。RANTES还被证明能激活高度纯化的嗜碱性粒细胞（纯度80%），其活性被多克隆抗RANTES抗体抑制。在次优浓度（6×10^(-9) M）下，RANTES不会使嗜碱性粒细胞致敏以增强诸如抗IgE、C5a或FMLP等促分泌剂诱导的组胺释放。另一方面，用RANTES或MCAF/MCP-1预孵育嗜碱性粒细胞会使嗜碱性粒细胞对这两种因子脱敏，但不会对抗IgE、C5a或FMLP脱敏。用百日咳毒素预孵育嗜碱性粒细胞会显著降低嗜碱性粒细胞对RANTES或MCAF/MCP-1的反应。这些结果表明RANTES和MCAF/MCP-1：1）是嗜碱性粒细胞的强效激活剂；2）可能通过嗜碱性粒细胞中相同或密切相关的受体系统发挥作用；3）可能代表了炎症性疾病如迟发相过敏反应中单核细胞、淋巴细胞和嗜碱性粒细胞激活之间的联系。
