Calgranulin B (S100A9/MRP14): a key molecule in idiopathic pulmonary fibrosis?
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.
Bargagli
Elena
E
Respiratory Diseases Section, Dept. of Clinical Medicine and Immunological Sciences, Siena University, Siena, Italy. bargagli2@gmail.com
Olivieri
Carmela
C
Cintorino
Marcella
M
Refini
Rosa M
RM
Bianchi
Nicola
N
Prasse
Antje
A
Rottoli
Paola
P
D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D040502:Calgranulin B / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D007958:Leukocyte Count; D008168:Lung / Q000737:chemistry / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology; D012129:Respiratory Function Tests; D012507:Sarcoidosis / Q000276:immunology*
D040502:Calgranulin B