Macrophage chitinase 1 stratifies chronic obstructive lung disease.
Diagnosis and therapy of chronic inflammatory lung disease is limited by the need for individualized biomarkers that provide insight into pathogenesis. Herein we show that mouse models of chronic obstructive lung disease exhibit an increase in lung chitinase production but cannot predict which chitinase family member may be equivalently increased in humans with corresponding lung disease. Moreover, we demonstrate that lung macrophage production of chitinase 1 is selectively increased in a subset of subjects with severe chronic obstructive pulmonary disease, and this increase is reflected in plasma levels. The findings provide a means to noninvasively track alternatively activated macrophages in chronic lung disease and thereby better differentiate molecular phenotypes in heterogeneous patient populations.
Agapov
Eugene
E
Department of Medicine, Washington University School of Medicine, Campus Box 8052, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Battaile
John T
JT
Tidwell
Rose
R
Hachem
Ramsey
R
Patterson
G Alexander
GA
Pierce
Richard A
RA
Atkinson
Jeffrey J
JJ
Holtzman
Michael J
MJ
D054392:Adipokines; D000368:Aged; D000818:Animals; D015415:Biomarkers; D000071451:Chitinase-3-Like Protein 1; D002688:Chitinases / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D006801:Humans; D018793:Interleukin-13 / Q000502:physiology; D037102:Lectins; D008168:Lung / Q000201:enzymology / Q000473:pathology; D016676:Macrophages, Alveolar / Q000201:enzymology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D010047:Ovalbumin / Q000633:toxicity; D010802:Phylogeny; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000145:classification / Q000201:enzymology* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D017386:Sequence Homology, Amino Acid; D012720:Severity of Illness Index; D012907:Smoking / Q000097:blood; D013045:Species Specificity
D054392:Adipokines; D015415:Biomarkers; C084533:CHI3L1 protein, human; C509289:Chil1 protein, mouse; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D018793:Interleukin-13; D037102:Lectins; D012333:RNA, Messenger; D010047:Ovalbumin; C499254:CHIA protein, human; D002688:Chitinases