Chemokine stromal cell-derived factor 1alpha activates basophils by means of CXCR4.
BACKGROUND
The CXC chemokine receptor 4 (CXCR4) is predominantly expressed on inactivated naive T lymphocytes, B lymphocytes, dendritic cells, and endothelial cells. CXC chemokine stromal cell-derived factor 1alpha (SDF-1alpha) is the only known ligand for CXCR4. To date, the CXCR4 expression and function of SDF-1alpha in basophils are unknown.


OBJECTIVE
The purpose of this study was to investigate the expression of CXCR4 and functions of SDF-1alpha in basophils and to characterize the role of the CXCR4-SDF-1alpha receptor ligand pair in the allergic inflammation.


METHODS
Basophil purification, flow cytometry, real-time quantitative RT-PCR assay, Northern blotting, intracellular free Ca(2+) change, chemotaxis assay, and histamine release assay were used.


RESULTS
CXCR4 is abundantly expressed on peripheral blood resting basophils (91%). Likewise, CXCR4 messenger (m)RNA is expressed in resting basophils (3.2 x 10(3) copies per 2 x 10(2) cells). The existence of CXCR4 mRNA was also confirmed in basophils by means of Northern blot analysis. SDF-1alpha induces an increase in intracellular free Ca(2+) in basophils. SDF-1alpha activates basophils to chemotaxis (chemotactic index = 3.8) and histamine release (36% of total content) through CXCR4 on the cells. The chemokines SDF-1alpha, eotaxin, RANTES, monocyte chemoattractant protein (MCP) 1, and macrophage inflammatory protein (MIP) 1alpha have been demonstrated at different potencies in induction of chemotaxis (eotaxin > SDF-1alpha > RANTES congruent with MCP-1 >> MIP-1alpha) and histamine release (MCP-1 congruent with SDF-1alpha > eotaxin > RANTES > MIP-1alpha). The optimal concentration seen for SDF-1alpha effects (chemotaxis and histamine release) on basophils was 100 ng/mL.


CONCLUSIONS
These results indicate that the CXCR4-SDF-1alpha receptor ligand pair may be important for the recruitment and activation of the basophils, which is a characteristic effector cell of the allergic inflammation.
Laboratory of Medical Allergology and the Reference Laboratory, Allergy Unit, National University Hospital, and the Department of Medical Physiology, University of Copenhagen, Copenhagen, Denmark.
T
T
Jinquan
H H
HH
Jacobi
C
C
Jing
C M
CM
Reimert
S
S
Quan
S
S
Dissing
L K
LK
Poulsen
P S
PS
Skov
D001491:Basophils / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000032:analysis; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000502:physiology*; D017154:Stromal Cells
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D002118:Calcium