Neutrophils as a Potential Source of Chitinase-3-like Protein 1 in Cystic Fibrosis

The chitinase-3-like protein 1, also known as YKL-40, is an inflammatory marker increased in blood of patients with cystic fibrosis (CF). Systemic levels of YKL-40 are increased in dysglycemic patients with CF. Our objective is to determine if YKL-40 is expressed and released by CF neutrophils. We also assessed if specific stimulus, such as glucose and lipopolysaccharide (LPS), can induce the secretion of YKL-40. Neutrophil cells of healthy adults and patients with CF were isolated. Immunostaining of whole blood and neutrophils was done. CF and healthy neutrophils were cultured with either LPS or varying concentrations of glucose. YKL-40 protein was measured using specific immunoassay ELISA. Isolated neutrophil cells from 11 patients with CF (32.3 ± 8.0 years) were compared to five age-matched healthy individuals (28.3 ± 5.5 years). Although there is a significant increase in the concentration of YKL-40 in CF neutrophils compared to healthy neutrophils (P = 0.027), the spontaneous release of YKL-40 into the media is similar in CF and healthy neutrophils. CF neutrophils stimulated with LPS or glucose do not stimulate the release of YKL-40 (P = 0.995 for glucose and P = 0.624 for LPS). CF neutrophils have higher intracellular level of YKL-40 than neutrophils from healthy volunteers, but they do not release more YKL-40 when stimulated with exogenous stimulus. These results suggest that the increased levels of circulating YKL-40 in CF patients might originate from another cellular source.