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Blood, 1 October 2002, Vol. 100, No. 7, pp. 2668-2671

BRIEF REPORT

Phagocytosing neutrophils down-regulate the expression of chemokine receptors CXCR1 and CXCR2

Tatyana Doroshenko, Yuri Chaly, Valery Savitskiy, Olga Maslakova, Anna Portyanko, Irina Gorudko, and Nikolai N. Voitenok

From the Laboratory of Cellular and Molecular Immunology, Institute of Hematology and Blood Transfusion; the Belarussian Center for Pediatric Oncology and Hematology; the Institute of Photobiology; the Belarussian State Medical University; and the Belarussian State University, Minsk, Belarus; and the Fund for Molecular Hematology and Immunology, Moscow, Russia.

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.

© 2002 by The American Society of Hematology.
 

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