Human peripheral blood eosinophils express a functional c-kit receptor for stem cell factor that stimulates very late antigen 4 (VLA-4)-mediated cell adhesion to fibronectin and vascular cell adhesion molecule 1 (VCAM-1)

被引:84
作者
Yuan, Q
Austen, KF
Friend, DS
Heidtman, M
Boyce, JA
机构
[1] HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115
[2] HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115
[3] BRIGHAM & WOMENS HOSP,DIV RHEUMATOL ALLERGY & IMMUNOL,BOSTON,MA 02115
[4] BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115
关键词
D O I
10.1084/jem.186.2.313
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
We evaluated mature peripheral blood eosinophils for their expression of the surface tyrosine kinase, c-kit, the receptor for the stromal cell-derived cytokine, stem cell factor (SCF). Cytofluorographic analysis revealed that c-kit was expressed on the purified peripheral blood eosinophils from 8 of 8 donors (4 nonatopic and 4 atopic) (mean channel fluorescence intensity 2.0-3.6-fold, average 2.8 +/- 0.6-fold, greater than the negative control). The uniform and selective expression of c-kit by eosinophils was confirmed by immunohistochemical analysis of peripheral blood buffy coats. The functional integrity of c-kit was demonstrated by the capacity of 100 ng/ml (5 nM) of recombinant human (rh) SCF to increase eosinophil adhesion to 3, 10, and 30 mu g/ml of immobilized FN40, a 40-kD chymotryptic fragment of plasma fibronectin, in 15 min by 7.7 +/- 1.4-, 5.3 +/- 3.3-, and 5.4 +/- 0.2-fold, respectively, and their adhesion to 0.1, 0.5, and 1.0 mu g/ml vascular cell adhesion molecule-1 (VCAM-1), by 12.7 +/- 9.2-, 3.8 +/- 2.5-, and 1.7 +/- 0.6-fold, respectively. The SCF-stimulated adhesion occurred without concomitant changes in surface integrin expression, thereby indicating an avidity-based mechanism. rhSCF (100 ng/ml, 5 nM) was comparable to rh eotaxin (200 ng/ml, 24 nM) in stimulating adhesion. Cell adhesion to FN40 was completely inhibited with antibodies against the alpha(4) and beta(1) integrin subunits, revealing that the SCF/c-kit adhesion effect was mediated by a single integrin heterodimer, very late antigen 4 (VLA-4). Thus, SCF represents a newly recognized stromal ligand for the activation of eosinophils for VLA-4-mediated adhesion, which could contribute to the exit of these cells from the blood, their tissue localization, and their prominence in inflammatory lesions.
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页码:313 / 323
页数:11
相关论文
共 77 条
[61]   ANTIBODY TO VERY LATE ACTIVATION ANTIGEN-4 PREVENTS ANTIGEN-INDUCED BRONCHIAL HYPERREACTIVITY AND CELLULAR INFILTRATION IN THE GUINEA-PIG AIRWAYS [J].
PRETOLANI, M ;
RUFFIE, C ;
SILVA, JRLE ;
JOSEPH, D ;
LOBB, RR ;
VARGAFTIG, BB .
JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 180 (03) :795-805
[62]   MECHANISMS OF EOSINOPHIL RECRUITMENT [J].
RESNICK, MB ;
WELLER, PF .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1993, 8 (04) :349-355
[63]   INVITRO ANTITUMOR-ACTIVITY OF EOSINOPHILS FROM CANCER-PATIENTS TREATED WITH SUBCUTANEOUS ADMINISTRATION OF INTERLEUKIN .2. ROLE OF INTERLEUKIN-5 [J].
RIVOLTINI, L ;
VIGGIANO, V ;
SPINAZZE, S ;
SANTORO, A ;
COLOMBO, MP ;
TAKATSU, K ;
PARMIANI, G .
INTERNATIONAL JOURNAL OF CANCER, 1993, 54 (01) :8-15
[64]  
ROTHENBERG ME, 1989, J IMMUNOL, V143, P2311
[65]   Strongyloides stercoralis: Eosinophil-dependent immune-mediated killing of third stage larvae in BALB/cByJ mice [J].
Rotman, HL ;
Yutanawiboonchai, W ;
Brigandi, RA ;
Leon, O ;
Gleich, GJ ;
Nolan, TJ ;
Schad, GA ;
Abraham, D .
EXPERIMENTAL PARASITOLOGY, 1996, 82 (03) :267-278
[66]  
Russell E S, 1979, Adv Genet, V20, P357, DOI 10.1016/S0065-2660(08)60549-0
[67]  
Saito H, 1996, J IMMUNOL, V157, P343
[68]   MECHANISM OF EOSINOPHILIA .5. KINETICS OF NORMAL AND ACCELERATED EOSINOPOIESIS [J].
SPRY, CJF .
CELL AND TISSUE KINETICS, 1971, 4 (04) :351-&
[69]  
TODD R, 1991, AM J PATHOL, V138, P1307
[70]   INDUCTION OF MAST-CELL PROLIFERATION, MATURATION, AND HEPARIN SYNTHESIS BY THE RAT C-KIT LIGAND, STEM-CELL FACTOR [J].
TSAI, M ;
TAKEISHI, T ;
THOMPSON, H ;
LANGLEY, KE ;
ZSEBO, KM ;
METCALFE, DD ;
GEISSLER, EN ;
GALLI, SJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (14) :6382-6386