Regulation of activin A expression in mast cells and asthma: Its effect on the proliferation of human airway smooth muscle cells

被引:83
作者
Cho, SH
Yao, ZB
Wang, SW
Alban, RF
Barbers, RG
French, SW
Oh, CK
机构
[1] Univ Calif Los Angeles, Harbor Med Ctr, Sch Med, Dept Pediat,Div Allergy & Immunol, Torrance, CA 90509 USA
[2] Univ Calif Los Angeles, Harbor Med Ctr, Sch Med, Dept Pathol, Torrance, CA 90509 USA
[3] Tanox Inc, Houston, TX USA
[4] Univ So Calif, Sch Med, Div Pulm & Crit Care Med, Los Angeles, CA 90033 USA
关键词
D O I
10.4049/jimmunol.170.8.4045
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Activin A, a homodimeric protein (betaAbetaA) and a member of the TGF-beta superfamily, is involved in the inflammatory repair process. Using cDNA microarray analysis, we discovered strong induction of the activin betaA gene in human mast cells (MC) on stimulation with PMA and calcium ionophore (A23187). Activin betaA mRNA was also highly induced in primary cultured murine bone marrow MC (BMMC) after stimulation by IgE receptor cross-linking. Secretion of activin A was evident in human mast cell-1 line cells 3 h after stimulation and progressively increased over time. Activin A was present in the cytoplasm of activated but not unstimulated murine bone marrow MC as demonstrated by immunofluorescence studies, suggesting that secretion of activin A by MC was due to de novo synthesis rather than secretion of preformed protein. Activin A also colocalized with human lung MC from patients with asthma by double-immunofluorescence staining. Furthermore, secretion of activin A was significantly increased in the airway of wild-type mice after OVA sensitization followed by intranasal challenge. Secretion of activin A, however, was greatly reduced in MC-deficient WBB6F(1)-W/W-v mice as compared with wild-type mice, indicating that MC are an important contributor of activin A in the airways of a murine asthma model. Additionally, activin A promoted the proliferation of human airway smooth muscle cells. Taken together, these data suggest that MC-derived activin A may play an important role in the process of airway remodeling by promoting the proliferation of airway smooth muscle.
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页码:4045 / 4052
页数:8
相关论文
共 57 条
[1]   Mast cell tryptase stimulates human lung fibroblast proliferation via protease-activated receptor-2 [J].
Akers, IA ;
Parsons, M ;
Hill, MR ;
Hollenberg, MD ;
Sanjar, S ;
Laurent, GJ ;
McAnulty, RJ .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2000, 278 (01) :L193-L201
[2]   Mast cell numbers are increased in the smooth muscle of human sensitized isolated bronchi [J].
Ammit, AJ ;
Bekir, SS ;
Johnson, PRA ;
Hughes, JM ;
Armour, CL ;
Black, JL .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1997, 155 (03) :1123-1129
[3]  
[Anonymous], SCH MIDDLE
[4]   THE MAST-CELL AND SIGNS OF PULMONARY FIBROBLAST ACTIVATION IN SARCOIDOSIS [J].
BJERMER, L ;
ENGSTROMLAURENT, A ;
THUNELL, M ;
HALLGREN, R .
INTERNATIONAL ARCHIVES OF ALLERGY AND APPLIED IMMUNOLOGY, 1987, 82 (3-4) :298-301
[5]  
Borgquist JD, 2002, J LEUKOCYTE BIOL, V71, P764
[6]   Asthma - From bronchoconstriction to airways inflammation and remodeling [J].
Bousquet, J ;
Jeffery, PK ;
Busse, WW ;
Johnson, M ;
Vignola, AM .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2000, 161 (05) :1720-1745
[7]   Mast-cell infiltration of airway smooth muscle in asthma [J].
Brightling, CE ;
Bradding, P ;
Symon, FA ;
Holgate, ST ;
Wardlaw, AJ ;
Pavord, ID .
NEW ENGLAND JOURNAL OF MEDICINE, 2002, 346 (22) :1699-1705
[8]  
BROIDE DH, 1990, J IMMUNOL, V145, P1838
[9]   MMP-2-and MMP-9-linked gelatinolytic activity in the sputum from patients with asthma and chronic obstructive pulmonary disease [J].
Cataldo, D ;
Munaut, C ;
Noël, A ;
Frankenne, F ;
Bartsch, P ;
Foidart, JM ;
Louis, R .
INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY, 2000, 123 (03) :259-267
[10]   Production of plasminogen activator inhibitor-1 by human mast cells and its possible role in asthma [J].
Cho, SH ;
Tam, SW ;
Demissie-Sanders, S ;
Filler, SA ;
Oh, CK .
JOURNAL OF IMMUNOLOGY, 2000, 165 (06) :3154-3161