Doroshenko Tatyana, Chaly Yuri, Savitskiy Valery, Maslakova Olga, Portyanko Anna, Gorudko Irina, Voitenok Nikolai N
Laboratory of Cellular and Molecular Immunology, Institute of Hematology and Blood Transfusion, Minsk, Belarus, Russia.
Blood. 2002 Oct 1;100(7):2668-71. doi: 10.1182/blood.100.7.2668.
CXC chemokines play a central role in regulation of neutrophil activation and chemotaxis. Because the chemotactic responses of neutrophils are impaired after phagocytosis, we explored the effect of phagocytic stimuli on the expression of interleukin-8 (IL-8) receptors, CXCR1 and CXCR2, in human neutrophils. After phagocytosis of opsonized yeast, the expression of CXCR1 and CXCR2 was substantially down-regulated and was accompanied by reduced Ca(++) responses to corresponding ligands, IL-8 and neutrophil-activating peptide-2 (NAP-2). The levels of CXCR1 and CXCR2 mRNA were constant during phagocytic stimulation of neutrophils. Confocal microscopy revealed that CXCR reduction was not via internalization. Metalloproteinase inhibitor, 1,10-phenantroline, prevented the reduction of CXCRs induced by phagocytosis, indicating that proteolytic degradation may be responsible for down-regulation. These observations suggest that down-regulation of CXCR expression may substantially reduce the responsiveness of phagocytosing neutrophils to CXC chemokines.
CXC趋化因子在中性粒细胞激活和趋化作用的调节中起核心作用。由于中性粒细胞吞噬后趋化反应受损，我们探讨了吞噬刺激对人中性粒细胞中白细胞介素8（IL-8）受体CXCR1和CXCR2表达的影响。吞噬调理酵母后，CXCR1和CXCR2的表达显著下调，并伴有对相应配体IL-8和中性粒细胞激活肽2（NAP-2）的Ca(++)反应降低。中性粒细胞吞噬刺激过程中CXCR1和CXCR2 mRNA水平保持恒定。共聚焦显微镜显示CXCR减少并非通过内化作用。金属蛋白酶抑制剂1,10-菲咯啉可阻止吞噬诱导的CXCR减少，表明蛋白水解降解可能是下调的原因。这些观察结果表明，CXCR表达下调可能会显著降低吞噬中的中性粒细胞对CXC趋化因子的反应性。
