Identification of selective basophil chemoattractants in human nasal polyps as insulin-like growth factor-1 and insulin-like growth factor-2
Identification of selective basophil chemoattractants in human nasal polyps as insulin-like growth factor-1 and insulin-like growth factor-2
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DOI：
10.4049/jimmunol.173.10.6448
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发表时间：
2004-11-15
影响因子：
4.4
通讯作者：
Williams, TJ
中科院分区：
文献类型：
--
作者：
Hartnell, A;Heinemann, A;Williams, TJ
在寻找变态反应性炎症部位的新型白细胞趋化剂时，我们在人鼻息肉的提取物中发现了嗜碱性粒细胞选择性趋化活性。提取物用反相高效液相色谱分离，得到的部分用灵敏的形状变化试验检测其刺激白细胞的活性。检测到的嗜碱性粒细胞选择活性不会被痘病毒CC-趋化因子结合蛋白亲和柱耗尽。用高效液相色谱对活性组分进行进一步纯化，并用串联电喷雾质谱对活性组份中的蛋白质进行分析。胰岛素样生长因子-2(IGF-2)存在于这些高效液相色谱组分中，其嗜碱性粒细胞刺激活性可被抗IGF-2中和抗体所抑制。重组IGF-2对嗜碱性粒细胞有明显的形状改变反应，但对嗜酸性粒细胞、中性粒细胞或单核细胞无明显影响。IGF-2刺激嗜碱性粒细胞趋化，但不刺激嗜酸性粒细胞或中性粒细胞趋化，并与嗜酸性粒细胞趋化因子-1/CCL11有协同作用。IGF-2还能上调嗜碱性粒细胞CD11b的表达，抑制细胞凋亡，但不能刺激脱颗粒或钙离子流。重组IGF-1对嗜碱性粒细胞的选择性作用与IGF-2相似，两种生长因子均可在鼻息肉提取液中检测到。这是化学动力因子增加嗜碱性粒细胞运动性的首次证明，但不作用于其他粒细胞或单核细胞。IGF-1和IGF-2可能在嗜碱性粒细胞体内选择性募集中发挥作用。
in a search for novel leukocyte chemoattractants at sites of allergic inflammation, we found basophil-selective chemoattractant activity in extracts of human nasal polyps. The extracts were fractionated by reverse phase HPLC, and the resulting fractions were tested for leukocyte-stimulating activity using sensitive shape change assays. The basophil-selective activity detected was not depleted by a poxvirus CC-chemokine-binding protein affinity column. This activity was further purified by HPLC, and proteins in the bioactive fractions were analyzed by tandem electrospray mass spectrometry. Insulin-like growth factor-2 (IGF-2) was identified in these HPLC fractions, and the basophil-stimulating activity was inhibited by an anti-IGF-2-neutralizing Ab. Recombinant IGF-2 induced a substantial shape change response in basophils, but not eosinophils, neutrophils, or monocytes. IGF-2 stimulated chemokinesis of basophils, but not eosinophils or neutrophils, and synergized with eotaxin-1/CCL11 in basophil chemotaxis. IGF-2 also caused up-regulation of basophil CD11b expression and inhibited apoptosis, but did not stimulate degranulation or Ca2+ flux. Recombinant IGF-1 exhibited similar basophil-selective effects as IGF-2, and both growth factors were detected in nasal polyp extracts by ELISA. This is the first demonstration of chemokinetic factors that increase the motility of basophils, but do not act on other granulocytes or *monocytes. IGF-1 and IGF-2 could play a role in the selective recruitment of basophils in vivo.