Localization of NUCB2/Nesfatin‐3/Nesfatin‐1 in Normal and Inflamed Human and Mouse Lungs, and Human Neutrophils

Abstract

Nesfatin‐1 regulates hunger and fat storage and is produced in the hypothalamus of mammals. Nucleobindin2 (NUCB2)/nesfatin‐1 protein expression in human plasma positively correlates with expression of pro‐inflammatory cytokines in patients with chronic obstructive pulmonary disease (COPD) suggesting its potential role in lung inflammation. However, we still don’t precisely know the expression of NUCB2/nesfatin‐1 in lungs and neutrophils. In this study, the expression of NUCB2/nesfatin‐3/nesfatin‐1 in normal and inflamed human and mouse lungs and neutrophils were examined with light and electron microscopic immunocytochemistry. Results from light microscopy showed that the localization of NUCB2/nesfatin‐1 in the pulmonary epithelium, alveolar septa, vascular endothelium and various immune cells does not change with inflammatory status. Electron microscopy revealed constitutive localization within the nucleus and cytoplasm of the aforementioned cells. Further, NUCB2/nesfatin‐1 accumulated within 0.5μm of the plasma membrane in human neutrophils following 90mins of 1ng/mL LPS stimulation. NUCB2/nesfatin‐3 was also found to localize in euchromatic portions of neutrophilic nuclei at 5 times the mean concentration compared to heterochromatin. Finally, our results indicate that NUCB2/nesfatin‐3 is predominantly cytoplasmic as it localizes at 2 times the concentration in neutrophilic cytoplasm compared to nucleus. Our study is the first to detail the localization of NUCB2/nesfatin‐1/nesfatin‐3 in lungs and neutrophils, and also implicate their potential role in transcriptional regulation.Support or Funding InformationNatural Sciences and Engineering Research Council of Canada