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.
Jinquan
T
T
Laboratory of Medical Allergology and the Reference Laboratory, Allergy Unit, National University Hospital, and the Department of Medical Physiology, University of Copenhagen, Copenhagen, Denmark.
Jacobi
H H
HH
Jing
C
C
Reimert
C M
CM
Quan
S
S
Dissing
S
S
Poulsen
L K
LK
Skov
P S
PS
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