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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.

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