The C-C chemokine receptor CCR3 participates in stimulation of eosinophil arrest on inflammatory endothelium in shear flow

被引:74
作者
Kitayama, J
Mackay, CR
Ponath, PD
Springer, TA
机构
[1] Ctr Blood Res, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
[3] LeukoSite Inc, Cambridge, MA 02142 USA
关键词
endothelium; eosinophils; eotaxin; chemokine receptor; very late antigen 4;
D O I
10.1172/JCI2688
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Chemokines are widely hypothesized to stimulate firm adhesion of leukocytes on endothelium in shear flow. Thus far, this has been demonstrated experimentally for exogenously added chemoattractants, but not for those released by endothelium. We found that human umbilical cord endothelial cells (HUVEC) stimulated with TNF-alpha and IFN-gamma secreted eosinophil chemoattractants into the culture supernatant. This material induced transendothelial chemotaxis, stimulated eosinophil binding to purified intercellular adhesion molecule 1, and augmented binding to purified vascular cell adhesion molecule 1 in a 3-min static assay. Chemotaxis and stimulation of adhesion were abrogated completely by the pretreatment of eosinophils with an mAb to the C-C chemokine receptor 3 (CCR3). Eosinophils accumulated efficiently on HUVEC stimulated with TNF-alpha and IFN-gamma in shear flow at 1.5 dyn/cm(2). CCR3 mAb slightly but significantly reduced eosinophil arrest and accumulation, by preventing development of firm adhesion by some of the tethered eosinophils, so that they detached within 30 s after the initial tethering. In the presence of mAb to the alpha 4 integrin subunit, the effect of CCR3 mAb was more prominent, and approximately half of eosinophil arrest and accumulation was abolished. Inhibition by CCR3 mAb in the presence of beta 2 integrin mAb was similar to that in control eosinophils. This is the first evidence that endothelial cell-derived chemokines can activate firm adhesion through alpha 4 and beta 2 integrins even in the presence of shear flow.
引用
收藏
页码:2017 / 2024
页数:8
相关论文
共 66 条
[1]   THE INTEGRIN VLA-4 SUPPORTS TETHERING AND ROLLING IN FLOW ON VCAM-1 [J].
ALON, R ;
KASSNER, PD ;
CARR, MW ;
FINGER, EB ;
HEMLER, ME ;
SPRINGER, TA .
JOURNAL OF CELL BIOLOGY, 1995, 128 (06) :1243-1253
[2]  
BAGGIOLINI M, 1994, ADV IMMUNOL, V55, P97
[3]   NEUTROPHIL-ACTIVATING PEPTIDE-1 INTERLEUKIN-8, A NOVEL CYTOKINE THAT ACTIVATES NEUTROPHILS [J].
BAGGIOLINI, M ;
WALZ, A ;
KUNKEL, SL .
JOURNAL OF CLINICAL INVESTIGATION, 1989, 84 (04) :1045-1049
[4]   CC-CHEMOKINES IN ALLERGIC INFLAMMATION [J].
BAGGIOLINI, M ;
DAHINDEN, CA .
IMMUNOLOGY TODAY, 1994, 15 (03) :127-133
[5]   ALPHA-4 INTEGRINS MEDIATE LYMPHOCYTE ATTACHMENT AND ROLLING UNDER PHYSIOLOGICAL FLOW [J].
BERLIN, C ;
BARGATZE, RF ;
CAMPBELL, JJ ;
VONANDRIAN, UH ;
SZABO, MC ;
HASSLEN, SR ;
NELSON, RD ;
BERG, EL ;
ERLANDSEN, SL ;
BUTCHER, EC .
CELL, 1995, 80 (03) :413-422
[6]   ADHESION OF HUMAN BASOPHILS, EOSINOPHILS, AND NEUTROPHILS TO INTERLEUKIN 1-ACTIVATED HUMAN VASCULAR ENDOTHELIAL-CELLS - CONTRIBUTIONS OF ENDOTHELIAL-CELL ADHESION MOLECULES [J].
BOCHNER, BS ;
LUSCINSKAS, FW ;
GIMBRONE, MA ;
NEWMAN, W ;
STERBINSKY, SA ;
DERSEANTHONY, CP ;
KLUNK, D ;
SCHLEIMER, RP .
JOURNAL OF EXPERIMENTAL MEDICINE, 1991, 173 (06) :1553-1556
[7]   EOSINOPHILIC INFLAMMATION IN ASTHMA [J].
BOUSQUET, J ;
CHANEZ, P ;
LACOSTE, JY ;
BARNEON, G ;
GHAVANIAN, N ;
ENANDER, I ;
VENGE, P ;
AHLSTEDT, S ;
SIMONYLAFONTAINE, J ;
GODARD, P ;
MICHEL, FB .
NEW ENGLAND JOURNAL OF MEDICINE, 1990, 323 (15) :1033-1039
[8]   LEUKOCYTE-ENDOTHELIAL CELL RECOGNITION - 3 (OR MORE) STEPS TO SPECIFICITY AND DIVERSITY [J].
BUTCHER, EC .
CELL, 1991, 67 (06) :1033-1036
[9]   TUMOR NECROSIS FACTOR/CACHECTIN STIMULATES PERITONEAL-MACROPHAGES, POLYMORPHONUCLEAR NEUTROPHILS, AND VASCULAR ENDOTHELIAL-CELLS TO SYNTHESIZE AND RELEASE PLATELET-ACTIVATING-FACTOR [J].
CAMUSSI, G ;
BUSSOLINO, F ;
SALVIDIO, G ;
BAGLIONI, C .
JOURNAL OF EXPERIMENTAL MEDICINE, 1987, 166 (05) :1390-1404
[10]   MONOCYTE CHEMOTACTIC PROTEIN-3 IS A MOST EFFECTIVE BASOPHIL-ACTIVATING AND EOSINOPHIL-ACTIVATING CHEMOKINE [J].
DAHINDEN, CA ;
GEISER, T ;
BRUNNER, T ;
VONTSCHARNER, V ;
CAPUT, D ;
FERRARA, P ;
MINTY, A ;
BAGGIOLINI, M .
JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 179 (02) :751-756