Monocyte chemotactic protein-4 (MCP-4; CCL-13): A biomarker of asthma

被引:57
作者
Kalayci, O
Sonna, LA
Woodruff, PG
Camargo, CA
Luster, AD
Lilly, CM
机构
[1] Harvard Univ, Div Pulm & Crit Care, Sch Med, Brigham & Womens Hosp,Channing Lab,Dept Med, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Brigham & Womens Hosp, Combined Program Pulm & Crit Care Med, Boston, MA 02115 USA
[3] USA, Environm Med Res Inst, Natick, MA 01760 USA
[4] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA
[5] Univ Calif San Francisco, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA
[6] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02115 USA
[7] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis,Div Rheumatol, Boston, MA 02115 USA
关键词
asthma; chemokine; biomarker; MCP-4; inflammation;
D O I
10.1081/JAS-120024590
中图分类号
R392 [医学免疫学];
学科分类号
100102 [免疫学];
摘要
Airway expression of monocyte chemotactic protein-4 (MCP-4; CCL-13) is known to be increased in asthmatic airways where it is induced by proallergic cytokines, but the relationship of its systemic expression to asthma and naturally occurring exacerbations is unknown. We determined plasma levels of MCP-4 in 356 individuals with chronic-stable asthma and 240 normal subjects and compared plasma levels of MCP-4 in 30 patients who presented for emergent treatment of asthma with levels in 90 subjects with chronic-stable asthma matched for age, gender, and ethnicity. Median plasma MCP-4 levels were higher in patients with chronic-stable asthma than in normal subjects (399 vs. 307 pg/mL) (p < 0.001). In our entire cohort (n = 596), subjects with an MCP-4 greater than or equal to 218 pg/mL were at increased risk of asthma (p < 0.001 odds ratio, 3.26; 95% Cl, 2.22-4.79). Logistic regression identified MCP-4 as an independent predictor of asthma diagnosis. The MCP-4 levels are higher in individuals with an acute asthma exacerbation than in subjects with chronic-stable asthma (513 vs. 355 pg/mL) (p = 0.002). The MCP-4 is a systemically expressed biomarker that independently predicts susceptibility to asthma and is directly associated with exacerbations. Elevated MCP-4 levels identify a group of asthmatics with systemic evidence of allergic inflammation who may be at risk for exacerbations or may benefit from abrogation of MCP-4.
引用
收藏
页码:27 / 33
页数:7
相关论文
共 24 条
[1]
LUNG-FUNCTION TESTING - SELECTION OF REFERENCE VALUES AND INTERPRETATIVE STRATEGIES [J].
不详 .
AMERICAN REVIEW OF RESPIRATORY DISEASE, 1991, 144 (05) :1202-1218
[2]
Cloning, in vitro expression, and functional characterization of a novel human CC chemokine of the monocyte chemotactic protein (MCP) family (MCP-4) that binds and signals through the CC chemokine receptor 2B [J].
Berkhout, TA ;
Sarau, HM ;
Moores, K ;
White, JR ;
Elshourbagy, N ;
Appelbaum, E ;
Reape, TJ ;
Brawner, M ;
Makwana, J ;
Foley, JJ ;
Schmidt, DB ;
Imburgia, C ;
McNulty, D ;
Matthews, J ;
ODonnell, K ;
OShannessy, D ;
Scott, M ;
Groot, PHE ;
Macphee, C .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (26) :16404-16413
[3]
Blanpain C, 1999, BLOOD, V94, P1899
[4]
Advances in immunology - Asthma [J].
Busse, WW ;
Lemanske, RF .
NEW ENGLAND JOURNAL OF MEDICINE, 2001, 344 (05) :350-362
[5]
Acute asthma among pregnant women presenting to the emergency department [J].
Cydulka, RK ;
Emerman, CL ;
Schreiber, D ;
Molander, KH ;
Woodruff, PG ;
Camargo, CA .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1999, 160 (03) :887-892
[6]
GarciaZepeda EA, 1996, J IMMUNOL, V157, P5613
[7]
Monocyte chemotactic protein-4: Tissue-specific expression and signaling through CC chemokine receptor-2 [J].
Godiska, R ;
Chantry, D ;
Raport, CJ ;
Schweickart, VL ;
LeTrong, H ;
Gray, PW .
JOURNAL OF LEUKOCYTE BIOLOGY, 1997, 61 (03) :353-360
[8]
Monocyte chemoattractant protein (MCP)-4 expression in the airways of patients with asthma - Induction in epithelial cells and mononuclear cells by proinflammatory cytokines [J].
Lamkhioued, B ;
Garcia-Zepeda, EA ;
Abi-Younes, S ;
Nakamura, H ;
Jedrzkiewicz, S ;
Wagner, L ;
Renzi, PM ;
Allakhverdi, Z ;
Lilly, C ;
Hamid, Q ;
Luster, AD .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2000, 162 (02) :723-732
[9]
Elevated plasma eotaxin levels in patients with acute asthma [J].
Lilly, CM ;
Woodruff, PG ;
Camargo, CA ;
Nakamura, H ;
Drazen, JM ;
Nadel, ES ;
Hanrahan, JP .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 1999, 104 (04) :786-790
[10]
Chemokines - Chemotactic cytokines that mediate inflammation [J].
Luster, AD .
NEW ENGLAND JOURNAL OF MEDICINE, 1998, 338 (07) :436-445