Calgranulin B (S100A9/MRP14): A Key Molecule in Idiopathic Pulmonary Fibrosis?

Abstract

Calgranulin B is a small calcium-binding protein with several immunological functions mainly involved in chronic inflammation and cancer. It can participate in recruitment of neutrophils and leukocytes in inflamed tissue, oxidant/antioxidant balance, adhesion of neutrophils to fibronectin, and regulation of apoptosis. In a previous proteomic study, we found that calgranulin B was up-regulated in the bronchoalveolar lavage (BAL) of patients with idiopathic pulmonary fibrosis (IPF) with respect to controls and patients with other interstitial lung diseases. The aims of this study are to compare calgranulin B concentrations in BAL of patients with IPF and sarcoidosis and controls by a quantitative method, to look for correlations with clinical data, and to evaluate calgranulin B expression in lung tissue of IPF patients by immunohistochemistry. A modification of a commercial ELISA was used to determine calgranulin B concentrations in BAL of 16 patients with IPF (a group of patients in which we previously performed proteomic analysis), 17 patients with sarcoidosis, and 7 controls. The immunohistochemistry was done in a subgroup of patients with IPF and a control group of lung transplant donors. Calgranulin B concentrations were significantly higher in patients with IPF than controls (p < 0.01); they were inversely correlated with FVC and DLCO values and directly correlated with neutrophil and eosinophil percentages in BAL. Immunohistochemistry revealed a patchy distribution of calgranulin B, predominantly around areas of fibrotic remodeling. Calgranulin B may be a trigger molecule involved in the evolution and progression of IPF, being overexpressed in BAL of patients with IPF with severe functional deterioration and in the peribronchiolar area bordering zones of honeycombing.

Migratory phase of Litomosoides sigmodontis filarial infective larvae is associated with pathology and transient increase of S100A9 expressing neutrophils in the lung

“…Intracellular proteins S100A8 and S100A9 belong to the large group of S100 calcium-binding proteins and form a heterodimer, calprotectin, (also called Mrp8/14-complex or S100A8/A9) which is abundant in neutrophils. This complex represents 40 to 60% of the neutrophil cytosolic granules content and has been shown to be present in lung pathologies [55–57] as well as in onchocercian nodules in which neutrophils are recruited [58]. Moreover, S100A8 and S100A9 are essential in the response to vascular injury [59] and this process is likely to happen in the lung of L .…”

Transcriptome analysis shows activation of circulating CD8+ T cells in patients with severe asthma

“…S100A8, S100A9, and S100A12, which were all shown to be upregulated in CD4 1 and CD8 1 T cells. Interestingly, increased calgranulin expression is linked to the development of rheumatoid arthritis, inflammatory bowel disease, and atherosclerosis 24,25 ;…”

S100A9 promotes human lung fibroblast cells activation through receptor for advanced glycation end-product-mediated extracellular-regulated kinase 1/2, mitogen-activated protein-kinase and nuclear factor-κB-dependent pathways

“…Bargagli et al . found that calgranulin B concentrations were higher in patients with IPF than controls and correlated directly with neutrophil and eosinophil percentages in BALF. In addition, calgranulin B was found to be up‐regulated in BALF of systemic sclerosis (SSc) patients with lung fibrosis compared to patients without pulmonary fibrosis .…”