A role for MCP-1/CCR2 in interstitial lung disease in children.
BACKGROUND
Interstitial lung diseases (ILD) are chronic inflammatory disorders leading to pulmonary fibrosis. Monocyte chemotactic protein 1 (MCP-1) promotes collagen synthesis and deletion of the MCP-1 receptor CCR2 protects from pulmonary fibrosis in ILD mouse models. We hypothesized that pulmonary MCP-1 and CCR2+ T cells accumulate in pediatric ILD and are related to disease severity.


METHODS
Bronchoalveolar lavage fluid was obtained from 25 children with ILD and 10 healthy children. Levels of pulmonary MCP-1 and Th1/Th2-associated cytokines were quantified at the protein and the mRNA levels. Pulmonary CCR2+, CCR4+, CCR3+, CCR5+ and CXCR3+ T cells were quantified by flow-cytometry.


RESULTS
CCR2+ T cells and MCP-1 levels were significantly elevated in children with ILD and correlated with forced vital capacity, total lung capacity and ILD disease severity scores. Children with lung fibrosis had significantly higher MCP-1 levels and CCR2+ T cells in bronchoalveolar lavage fluid compared to non-fibrotic children.


CONCLUSIONS
The results indicate that pulmonary CCR2+ T cells and MCP-1 contribute to the pathogenesis of pediatric ILD and might provide a novel target for therapeutic strategies.
Hartl
Dominik
D
Childrens' Hospital, Ludwig-Maximilians-University, Munich, Germany. dominic.hartl@med.uni-muenchen.de
Griese
Matthias
M
Nicolai
Thomas
T
Zissel
Gernot
G
Prell
Christine
C
Reinhardt
Dietrich
D
Schendel
Dolores J
DJ
Krauss-Etschmann
Susanne
S
D000293:Adolescent; D001249:Asthma / Q000378:metabolism* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D018932:Chemokine CCL2 / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000378:metabolism* / Q000473:pathology; D008297:Male; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000378:metabolism*; D012720:Severity of Illness Index; D018417:Th1 Cells / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000378:metabolism / Q000473:pathology
C111835:CCL2 protein, human; C515334:CCR2 protein, human; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D054390:Receptors, CCR2; D019707:Receptors, Chemokine