Kuna P, Reddigari S R, Rucinski D, Schall T J, Kaplan A P
Department of Medicine, State University of New York-Stony Brook 11794-8160.
J Allergy Clin Immunol. 1995 Feb;95(2):574-86. doi: 10.1016/s0091-6749(95)70320-9.
Monocyte chemotactic and activating factor (MCAF) is the most potent cytokine that activates basophils to release histamine. The response of human basophils to either simultaneous or sequential addition of the chemokines RANTES, macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, platelet factor (PF)4, connective tissue activating peptide III (CTAP-III), interleukin (IL)-8, and inflammatory protein (IP)-10 on MCAF-induced histamine release was studied. Simultaneous addition of MCAF and any of the chemokines studied evoked an augmented response as measured by histamine release, whereas preincubation of leukocytes or purified basophils (80%) with these chemokines decreased MCAF-induced histamine release in a dose-dependent manner. Histamine release by anti-IgE remained unchanged. When tested at 5 x 10(-9) mol/L, the decrease in histamine release by RANTES was 69.2% +/- 3.5%, by MIP-1 alpha 48.8% +/- 3.1%, by MIP-1 beta 42.9% +/- 3.1%, by PF4 56.5% +/- 2.9%, by IL-8 41.2% +/- 2.2, by CTAP III 27% +/- 4.4%, and by IP-10 15.3% +/- 2.6%. The peak inhibition of histamine release by the chemokines was reached within 10 minutes of preincubation with basophils and remained unchanged thereafter. Washing basophils after preincubation with chemokines abolished the inhibition, with the exception of desensitization by low concentrations of MCAF. With the exclusion of MCAF and RANTES, none of the chemokines (at the concentration range of 5 x 10(-8) to 5 x 10(-11)) induced significant (> 10% above spontaneous) histamine release from basophils. Preincubation of basophils with C5a (5 x 10(-10) mol/L) did not affect histamine release, whereas preincubation with granulocyte-macrophage colony-stimulating factor (10 ng/ml) or IL-5 (10 ng/ml) enhanced MCAF-induced histamine release by 121.8% +/- 10.1% and 108% +/- 10.8%, respectively. We have therefore characterized RANTES, MIP-1 alpha, MIP-1 beta, CTAP III, PF4, IL-8, and IP-10 as inhibitors of MCAF-induced histamine release. Although the results are consistent with receptor blockade, the alpha and beta chemokines appear to interact with separate receptors linked to G proteins; thus, a mechanism of receptor class desensitization is proposed. Interaction of this group of cytokines at the site of allergic inflammation may modulate a function of basophils to initiate, augment, or inhibit histamine release.
单核细胞趋化激活因子（MCAF）是激活嗜碱性粒细胞释放组胺的最有效细胞因子。研究了人嗜碱性粒细胞对趋化因子RANTES、巨噬细胞炎性蛋白（MIP）-1α、MIP-1β、血小板因子（PF）4、结缔组织激活肽III（CTAP-III）、白细胞介素（IL）-8和炎性蛋白（IP）-10同时或先后添加对MCAF诱导的组胺释放的反应。同时添加MCAF和任何一种所研究的趋化因子，通过组胺释放测量可引起增强反应，而用这些趋化因子对白细胞或纯化的嗜碱性粒细胞（80%）进行预孵育，则以剂量依赖方式降低MCAF诱导的组胺释放。抗IgE诱导的组胺释放保持不变。当在5×10⁻⁹mol/L进行测试时，RANTES使组胺释放减少69.2%±3.5%，MIP-1α减少48.8%±3.1%，MIP-1β减少42.9%±3.1%，PF4减少56.5%±2.9%，IL-8减少41.2%±2.2%，CTAP III减少27%±4.4%，IP-10减少15.3%±2.6%。趋化因子对组胺释放的抑制峰值在与嗜碱性粒细胞预孵育10分钟内达到，此后保持不变。用趋化因子预孵育后洗涤嗜碱性粒细胞可消除抑制作用，但低浓度MCAF引起的脱敏作用除外。除MCAF和RANTES外，在所研究的趋化因子（浓度范围为5×10⁻⁸至5×10⁻¹¹）中，没有一种能诱导嗜碱性粒细胞释放显著（高于自发释放10%以上）的组胺。用C5a（5×10⁻¹⁰mol/L）对嗜碱性粒细胞进行预孵育不影响组胺释放，而用粒细胞-巨噬细胞集落刺激因子（10 ng/ml）或IL-5（10 ng/ml）进行预孵育分别使MCAF诱导的组胺释放增加121.8%±10.1%和108%±10.8%。因此，我们已将RANTES、MIP-1α、MIP-1β、CTAP III、PF4、IL-8和IP-10鉴定为MCAF诱导的组胺释放的抑制剂。尽管结果与受体阻断一致，但α和β趋化因子似乎与连接到G蛋白的不同受体相互作用；因此，提出了一种受体类别脱敏机制。这组细胞因子在变应性炎症部位的相互作用可能调节嗜碱性粒细胞启动、增强或抑制组胺释放的功能。
