Inhibition of stem cell factor reduces pulmonary cytokine levels during allergic airway responses

被引:26
作者
Berlin, AA
Lincoln, P
Tomkinson, A
Lukacs, NW
机构
[1] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA
[2] Bayer Biotechnol, Berkeley, CA USA
关键词
asthma; cytokines; mucus; stem cell factor;
D O I
10.1111/j.1365-2249.2004.02404.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Stem cell factor (SCF) has a significant role in the inflammation and activation of allergic airway responses. When monoclonal anti-SCF was administered intratracheally during allergen challenge there was a significant alteration of eosinophil accumulation and airway hyperreactivity (AHR). Anti-SCF treatment also attenuated pulmonary cytokine and chemokine levels. In particular, there was an antibody dose-dependent decrease in interleukin (IL)-5 and tumour necrosis factor (TNF)-alpha. There was also a significant reduction of CCL2 and CCL5, which correlated with the reduction in AHR. Mice treated with anti-SCF demonstrated a significant decrease in pulmonary gob-5 gene expression, which has been shown to correlate to goblet cell hyperplasia/metaplasia relating to airway mucus production. Blocking SCF-mediated activation within the airway using a monoclonal antibody indicates that this cytokine may represent a viable target for therapeutic intervention that could affect multiple aspects of allergen-induced immunopathology.
引用
收藏
页码:15 / 20
页数:6
相关论文
共 59 条
[51]   CC chemokines and interleukin-5 in bronchial lavage fluid from patients with status asthmaticus - Potential implication in eosinophil recruitment [J].
Tillie-Leblond, I ;
Hammad, H ;
Desurmont, S ;
Pugin, J ;
Wallaert, B ;
Tonnel, AB ;
Gosset, P .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2000, 162 (02) :586-592
[52]   A calcium-activated chloride channel (HCLCA1) is strongly related to IL-9 expression and mucus production in bronchial epithelium of patients with asthma [J].
Toda, M ;
Tulic, MK ;
Levitt, RC ;
Hamid, Q .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2002, 109 (02) :246-250
[53]  
Tournoy KG, 2000, CLIN EXP ALLERGY, V30, P79
[54]   THE RAT C-KIT LIGAND, STEM-CELL FACTOR, INDUCES THE DEVELOPMENT OF CONNECTIVE-TISSUE TYPE AND MUCOSAL MAST-CELLS INVIVO - ANALYSIS BY ANATOMICAL DISTRIBUTION, HISTOCHEMISTRY, AND PROTEASE PHENOTYPE [J].
TSAI, M ;
SHIH, LS ;
NEWLANDS, GFJ ;
TAKEISHI, T ;
LANGLEY, KE ;
ZSEBO, KM ;
MILLER, HRP ;
GEISSLER, EN ;
GALLI, SJ .
JOURNAL OF EXPERIMENTAL MEDICINE, 1991, 174 (01) :125-131
[55]   RECOMBINANT STEM-CELL FACTOR-INDUCED MAST-CELL ACTIVATION AND SMOOTH-MUSCLE CONTRACTION IN HUMAN BRONCHI [J].
UNDEM, BJ ;
LICHTENSTEIN, LM ;
HUBBARD, WC ;
MEEKER, S ;
ELLIS, JL .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1994, 11 (06) :646-650
[56]   Mast cell-derived TNF-α primes sensory nerve endings in a pulmonary hypersensitivity reaction [J].
van Houwelingen, AH ;
Kool, M ;
de Jager, SCA ;
Redegeld, FAM ;
van Heuven-Nolsen, D ;
Kraneveld, AD ;
Nijkamp, FP .
JOURNAL OF IMMUNOLOGY, 2002, 168 (10) :5297-5302
[57]   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) [J].
Yuan, Q ;
Austen, KF ;
Friend, DS ;
Heidtman, M ;
Boyce, JA .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 186 (02) :313-323
[58]  
Zhang S, 1996, J PATHOL, V180, P95
[59]   Characterization of a calcium-activated chloride channel as a shared target of Th2 cytokine pathways and its potential involvement in asthma [J].
Zhou, YH ;
Dong, Q ;
Louahed, J ;
Dragwa, C ;
Savio, D ;
Huang, MX ;
Weiss, C ;
Tomer, Y ;
McLane, MP ;
Nicolaides, NC ;
Levitt, RC .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2001, 25 (04) :486-491