Surface expression of neutrophil CXCR4 is down-modulated by bacterial endotoxin.
The chemokine receptor CXCR4 and its unique ligand, stromal-derived factor 1 (SDF-1), play critical roles in the retention of hematopoietic cells within bone marrow and in their mobilization into the circulation. Surface CXCR4 down-regulation in hematopoietic cells is associated with a loss of retention of the cells in bone marrow. Lipopolysaccharide (LPS), commonly referred to as endotoxin, induces neutrophilia in vivo, but the mechanism of mobilization related to neutrophilia has not been fully clarified. We show that LPS reduces CXCR4 surface expression in a dose- and time-dependent manner in neutrophils and monocytes, but not in lymphocytes. Polymyxin B neutralization of LPS in culture supernatants still induced this down-modulation, and LPS-stimulated neutrophils released interferon gamma and interleukin 1beta. These results provide evidence that CXCR4 down-regulation can be attributed to soluble factors released by neutrophils upon LPS treatment. Moreover, LPS treatment increased CXCR4 messenger RNA in neutrophils, suggesting that the down-regulation of surface CXCR4 is caused by a posttranslational mechanism, and the chemotactic migration of neutrophils in response to SDF-1 was reduced by LPS pretreatment. Thus, the present study has shown that by down-regulating neutrophil CXCR4 expression and attenuating neutrophil responsiveness to SDF-1, LPS can mobilize neutrophils from bone marrow to the peripheral blood through reducing neutrophil retention in bone marrow.
Kim
Hyun Kyung
HK
Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.
Kim
Ji-Eun
JE
Chung
Junho
J
Han
Kyou-Sup
KS
Cho
Han-Ik
HI
D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D008070:Lipopolysaccharides; D019718:Receptors, CXCR4; D011956:Receptors, Cell Surface