Phagocytosing neutrophils down-regulate the expression of chemokine receptors CXCR1 and CXCR2.
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.
Doroshenko
Tatyana
T
Laboratory of Cellular and Molecular Immunology, Institute of Hematology and Blood Transfusion, Minsk, Belarus, Russia.
Chaly
Yuri
Y
Savitskiy
Valery
V
Maslakova
Olga
O
Portyanko
Anna
A
Gorudko
Irina
I
Voitenok
Nikolai N
NN
D002118:Calcium / Q000097:blood; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D003600:Cytosol / Q000502:physiology; D015536:Down-Regulation; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D018613:Microscopy, Confocal; D009504:Neutrophils / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D010587:Phagocytosis / Q000502:physiology*; D023062:Receptors, Interleukin-8A / Q000235:genetics*; D023063:Receptors, Interleukin-8B / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000502:physiology
D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D002118:Calcium