Chemokine receptor expression profile of eosinophils at inflamed tissue sites: Decreased CCR3 and increased CXCR4 expression by lung eosinophils.
BACKGROUND
To date, most studies dealing with eosinophil chemokine receptors have used eosinophils isolated from peripheral blood. During the movement of eosinophils from the peripheral blood to inflamed tissue sites, microenvironmental signals might alter their expression of chemokine receptors. However, little is known about the profile of expression of chemokine receptors by eosinophils at inflamed tissue sites in human beings.


OBJECTIVE
The purpose of this study was to determine whether eosinophils that have migrated into inflamed tissues exhibit a profile of chemokine receptor expression that is qualitatively and/or quantitatively different from that of eosinophils in peripheral locations.


METHODS
We studied simultaneously the expression and function of chemokine receptors in eosinophils in both bronchoalveolar lavage fluid (BALF) and peripheral blood specimens of 7 patients with eosinophilic lung diseases.


RESULTS
De novo expression of CCR2, CCR4, and CCR5 was not detected at either the protein or the mRNA level. However, surface expression of CCR3 was decreased and CXCR4 was conversely increased with statistical significance in BALF eosinophils. Moreover, the changes in CCR3 and CXCR4 expression were reflected in the altered migratory response to their ligands. On the other hand, the levels of CXCR1, CXCR2, CXCR3, and CCR1 were virtually unchanged in BALF eosinophils, and these receptors did not have functional significance.


CONCLUSIONS
Eosinophils at inflamed tissue sites exhibited an expression profile qualitatively similar to that in peripheral locations, except for decreased CCR3 and increased CXCR4 expression. Our results suggest that CCR3 is primarily and CXCR4 is cooperatively involved in eosinophil accumulation at inflamed tissue sites.
Nagase
H
H
Department of Respiratory Medicine, University of Tokyo Graduate School of Medicine, Japan.
Kudo
K
K
Izumi
S
S
Ohta
K
K
Kobayashi
N
N
Yamaguchi
M
M
Matsushima
K
K
Morita
Y
Y
Yamamoto
K
K
Hirai
K
K
D000328:Adult; D000368:Aged; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000276:immunology; D001249:Asthma / Q000276:immunology; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011657:Pulmonary Eosinophilia / Q000276:immunology*; D054397:Receptors, CCR3; D019718:Receptors, CXCR4 / Q000302:isolation & purification*; D019707:Receptors, Chemokine / Q000302:isolation & purification*
C515350:CCR3 protein, human; D054397:Receptors, CCR3; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine