TNF alpha is important in human lung allergic reactions

被引:60
作者
Casale, TB
Costa, JJ
Galli, SJ
机构
[1] UNIV IOWA, COLL MED, IOWA CITY, IA USA
[2] VET AFFAIRS MED CTR, DEPT INTERNAL MED, IOWA CITY, IA 52242 USA
[3] BETH ISRAEL HOSP, DEPT PATHOL, BOSTON, MA 02215 USA
[4] HARVARD UNIV, SCH MED, BOSTON, MA USA
关键词
D O I
10.1165/ajrcmb.15.1.8679220
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Tumor necrosis factor alpha (TNF alpha) is a potentially important cytokine in allergic respiratory reactions since it is released by mast cells and eosinophils, and it can promote mediator and cytokine release, adhesion molecule expression, and granulocyte migration. Therefore, we induced an IgE-mediated response in human lung samples and studied: (1) whether TNF alpha was produced in sufficient quantities to promote granulocyte migration; and (2) which cells expressed mRNA for TNF alpha using in situ hybridization. Lung fragments (from thoracotomy) were treated for 30 min with either anti-IgE, 1:100 dilution, or buffer (control). Anti-IgE treatment of 16 lungs resulted in greater than 4-fold increase in histamine release and the significant production of chemotactic activity. The chemotactic activity generated induced dose-responsive neutrophil and eosinophil migration through naked filters and endothelial and pulmonary epithelial monolayers. Fourteen of 16 samples had a significant increase in TNF alpha subsequent to anti-IgE treatment (P < 0.05). Anti-TNF alpha antibody (4 mu g/ml) inhibited about 25% of the neutrophil chemotactic activity in supernatants from anti-IgE treated lungs. TNF alpha at a concentration measured after anti-IgE treatment of lung samples (50 pg/ml) induced neutrophil transendothelial migration. Finally, we found that anti-IgE treatment led to an increase in TNF alpha mRNA-positive cells by in situ hybridization (1.6/ mm(2) experimental versus 0.5/mm(2) control), some of which were eosinophils. Thus, human lung IgE-mediated responses in vitro results in: (1) release of TNF alpha in amounts sufficient to effect a biologic response, granulocyte chemotaxis; and (2) upregulation of mRNA for TNF alpha in eosinophils and other cells. These findings suggest that TNF alpha is an important effector molecule in the pathogenesis of allergic respiratory reactions.
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收藏
页码:35 / 44
页数:10
相关论文
共 35 条
[1]   ENDOTHELIAL AND EPITHELIAL-CELL ADHESION MOLECULES [J].
ALBELDA, SM .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1991, 4 (03) :195-203
[2]  
BITTERMAN DB, 1994, AM J RESPIR CARE M 2, V149, pA116
[3]   ALLERGIC MODELS AND CYTOKINES [J].
BITTLEMAN, DB ;
CASALE, TB .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1994, 150 (05) :S72-S76
[4]   INTERLEUKIN-4, INTERLEUKIN-5, AND INTERLEUKIN-6 AND TUMOR-NECROSIS-FACTOR-ALPHA IN NORMAL AND ASTHMATIC AIRWAYS - EVIDENCE FOR THE HUMAN MAST-CELL AS A SOURCE OF THESE CYTOKINES [J].
BRADDING, P ;
ROBERTS, JA ;
BRITTEN, KM ;
MONTEFORT, S ;
DJUKANOVIC, R ;
MUELLER, R ;
HEUSSER, CH ;
HOWARTH, PH ;
HOLGATE, ST .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1994, 10 (05) :471-480
[5]   CYTOKINES IN SYMPTOMATIC ASTHMA AIRWAYS [J].
BROIDE, DH ;
LOTZ, M ;
CUOMO, AJ ;
COBURN, DA ;
FEDERMAN, EC ;
WASSERMAN, SI .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 1992, 89 (05) :958-967
[6]  
Burd PR, 1994, HUMAN CYTOKINES THEI, P87
[7]  
CAPRON M, 1981, J IMMUNOL, V126, P2087
[8]   DIRECT EVIDENCE OF A ROLE FOR MAST-CELLS IN THE PATHOGENESIS OF ANTIGEN-INDUCED BRONCHOCONSTRICTION [J].
CASALE, TB ;
WOOD, D ;
RICHERSON, HB ;
ZEHR, B ;
ZAVALA, D ;
HUNNINGHAKE, GW .
JOURNAL OF CLINICAL INVESTIGATION, 1987, 80 (05) :1507-1511
[9]   ACUTE EFFECTS OF INVITRO MAST-CELL DEGRANULATION ON HUMAN LUNG MUSCARINIC RECEPTORS [J].
CASALE, TB .
AMERICAN REVIEW OF RESPIRATORY DISEASE, 1993, 147 (04) :940-945
[10]   HUMAN EOSINOPHILS CAN EXPRESS THE CYTOKINES TUMOR-NECROSIS-FACTOR-ALPHA AND MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA [J].
COSTA, JJ ;
MATOSSIAN, K ;
RESNICK, MB ;
BEIL, WJ ;
WONG, DTW ;
GORDON, JR ;
DVORAK, AM ;
WELLER, PF ;
GALLI, SJ .
JOURNAL OF CLINICAL INVESTIGATION, 1993, 91 (06) :2673-2684