Depletion of eosinophils in mice through the use of antibodies specific for C-C chemokine receptor 3 (CCR3)

被引:75
作者
Grimaldi, JC [1 ]
Yu, NX [1 ]
Grunig, G [1 ]
Seymour, BWP [1 ]
Cottrez, F [1 ]
Robinson, DS [1 ]
Hosken, N [1 ]
Ferlin, WG [1 ]
Wu, XY [1 ]
Soto, H [1 ]
O'Garra, A [1 ]
Howard, MC [1 ]
Coffman, RL [1 ]
机构
[1] DNAX Res Inst Mol & Cellular Biol Inc, Palo Alto, CA 94304 USA
关键词
rodent; FACS; Th1; Th2;
D O I
10.1002/jlb.65.6.846
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
We have generated rat monoclonal antibodies specific for the mouse eotaxin receptor, C-C chemokine receptor 3 (CCR3). Several anti-CCR3 mAbs proved to be useful for in vivo depletion of CCR3-expressing cells and immunofluorescent staining. In vivo CCR3 mAbs of the IgG2b isotype substantially depleted blood eosinophil levels in Nippostrongyus brasiliensis-infected mice. Repeated anti-CCR3 mAb treatment in these mice significantly reduced tissue eosinophilia in the lung tissue and bronchoalveolar lavage fluid. Flow cytometry revealed that mCCR3 was expressed on eosinophils but not on stem cells, dendritic cells, or cells from the thymus, lymph node, or spleen of normal mice. Unlike human Th2 cells, mouse Th2 cells did not express detectable levels of CCR3 nor did they give a measurable response to eotaxin. None of the mAbs were antagonists or agonists of CCR3 calcium mobilization. To our knowledge, the antibodies described here are the first mAbs reported to be specific for mouse eosinophils and to be readily applicable for the detection, isolation, and in vivo depletion of eosinophils.
引用
收藏
页码:846 / 853
页数:8
相关论文
共 27 条
[1]   A new class of membrane-bound chemokine with a CX(3)C motif [J].
Bazan, JF ;
Bacon, KB ;
Hardiman, G ;
Wang, W ;
Soo, K ;
Rossi, D ;
Greaves, DR ;
Zlotnik, A ;
Schall, TJ .
NATURE, 1997, 385 (6617) :640-644
[2]   Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s [J].
Bonecchi, R ;
Bianchi, G ;
Bordignon, PP ;
D'Ambrosio, D ;
Lang, R ;
Borsatti, A ;
Sozzani, S ;
Allavena, P ;
Gray, PA ;
Mantovani, A ;
Sinigaglia, F .
JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 187 (01) :129-134
[3]   Cloning, expression, and characterization of the human eosinophil eotaxin receptor [J].
Daugherty, BL ;
Siciliano, SJ ;
DeMartino, JA ;
Malkowitz, L ;
Sirotina, A ;
Springer, MS .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 183 (05) :2349-2354
[4]   Eotaxin-2, a novel CC chemokine that is selective for the chemokine receptor CCR3, and acts like eotaxin on human eosinophil and basophil leukocytes [J].
Forssmann, U ;
Uguccioni, M ;
Loetscher, P ;
Dahinden, CA ;
Langen, H ;
Thelen, M ;
Baggiolini, M .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 185 (12) :2171-2176
[5]   Mouse eotaxin expression parallels eosinophil accumulation during lung allergic inflammation but it is not restricted to a Th2-type response [J].
Gonzalo, JA ;
Jia, GQ ;
Aguirre, V ;
Friend, D ;
Coyle, AJ ;
Jenkins, NA ;
Lin, GS ;
Katz, H ;
Lichtman, A ;
Copeland, N ;
Kopf, M ;
GutierrezRamos, JC .
IMMUNITY, 1996, 4 (01) :1-14
[6]   Chemokine receptor usage by human eosinophils - The importance of CCR3 demonstrated using an antagonistic monoclonal antibody [J].
Heath, H ;
Qin, SX ;
Rao, P ;
Wu, LJ ;
LaRosa, G ;
Kassam, N ;
Ponath, PD ;
Mackay, CR .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 99 (02) :178-184
[7]   Chemokines and lymphocyte biology [J].
Hedrick, JA ;
Zlotnik, A .
CURRENT OPINION IN IMMUNOLOGY, 1996, 8 (03) :343-347
[8]  
Hedrick JA, 1997, J IMMUNOL, V158, P1533
[9]   EOTAXIN - CLONING OF AN EOSINOPHIL CHEMOATTRACTANT CYTOKINE AND INCREASED MESSENGER-RNA EXPRESSION IN ALLERGEN-CHALLENGED GUINEA-PIG LUNGS [J].
JOSE, PJ ;
ADCOCK, IM ;
GRIFFITHSJOHNSON, DA ;
BERKMAN, N ;
WELLS, TNC ;
WILLIAMS, TJ ;
POWER, CA .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1994, 205 (01) :788-794
[10]   EOSINOPHILS AND NEUTROPHILS [J].
KAY, AB ;
CORRIGAN, CJ .
BRITISH MEDICAL BULLETIN, 1992, 48 (01) :51-64