Chitinases and Chitinase-Like Proteins in Obstructive Lung Diseases – Current Concepts and Potential Applications

Figures & data

Figure 1 Schematic depiction of chitin, chitinases and chitinase-like proteins (CLPs) involvement in lung diseases.

Notes: Exposure to chitin may trigger the secretion of chitinases and CLPs from neutrophils, macrophages and other cells (solid-line black arrows show cell activation after chitin exposure and secretion of chitinases). Both groups of enzymes are thought to play a role in the pathogenesis of pulmonary diseases (eg, asthma and COPD). Black dashed arrows reflect a negative (ie, destructive) effect, while the grey dashed arrows show a possible positive (ie, protective) influence. See manuscript text for more details.

Figure 2 Schematic presentation of the hypothesized links between chitotriosidase (CHIT1) and the pathogenesis of lung inflammation and injury (eg, in COPD).

Notes: The exposure to cigarette smoke and other factors may enhance CHIT1 expression and increase its production, mainly by lung macrophages and neutrophils. The impact of CHIT1 on lung cells is heterogeneous and include inflammation and tissue destruction, mediated by interleukin 8 (IL-8), metalloproteinase 9 (MMP-9) and monocyte chemoattractant protein 1 (MCP-1), as well as lung fibrosis induced by transforming growth factor-beta (TGF-β) pathway. However, the exact role of CHIT1 in the pathogenesis of lung diseases is still highly hypothetical. A large white arrow represents stimulation of macrophages and neutrophils by various factors, the thick grey arrows show the secretion of CHIT1 from the cellular sources, the thin black arrows depict the pathways of CHIT1 activity, the vertical yellow arrow represents the increase or enhancement.

Figure 3 Schematic representation of the supposed mechanisms involved in YKL-40-related emphysematous lung destruction, tissue inflammation and remodeling.

Notes: The large white arrow represents stimulation of macrophages, epithelial cells and neutrophils by various factors, the thin dashed black arrow depicts an indirect effect of environmental factors, the thick grey arrows show the secretion of YKL-40 from the cellular sources, the thin black arrows depict the possible YKL-40 signaling pathways, the thin dashed grey arrow depicts a stimulatory effect of interleukin 13 (IL-13) on transforming growth factor-beta (TGFβ), the vertical yellow arrow represents the increase or enhancement. See manuscript text for more details.

Table 1 Selected Information About Main Chitinases and Their Role in Humans

Type of Chitinase/CLP	Source	Known Stimuli Increasing Expression and Release	Known or Potential Conditions Associated with Abnormal Release	Role
Chitotriosidase (CHIT1)	Macrophages, neutrophils, epithelial cells	IFN-γ, TNF-α, GM-CSF, TLR stimulation	Lysosomal storage diseases, neurodegenerative diseases (eg, Alzheimer’s disease), acute infections (fungal and bacterial) chronic inflammation (eg, sarcoidosis), others (eg, non-alcoholic fatty liver disease)	Hydrolysis of chitin, trans-glycosylation activity, enhancement of immune response
AMCase	Lung epithelial cells, macrophages, eosinophils	IL-13, EGFR stimulation, TACE	Asthma, allergy	Hydrolysis of chitin, trans-glycosylation, Th2 inflammatory response,
YKL-40	Chondrocytes, synovial cells, macrophages, fibroblasts, neutrophils, epithelial cells	IL-6, IFN-γ, AVP, PTHrP	Acute infections (eg, pneumonia), chronic inflammatory conditions (eg, asthma/allergy, COPD, sarcoidosis) cancers (eg, osteosarcoma, glioblastoma, breast cancer) others (eg, liver fibrosis, schizophrenia)	No chitinase activity, role in inflammation, tissue remodeling, and degradation

Abbreviations: AVP, arginine-vasopressin; COPD, chronic obstructive pulmonary disease; DM2, diabetes mellitus type 2; GM-CSF, granulocyte-macrophage colony-stimulating factor; IFN-γ, interferon-gamma; IL, interleukin; PTHrP, parathyroid hormone-related protein; TACE, TNF-α-converting enzyme; TLR, Toll-like receptor; TNFα, tumor necrosis factor α.