Influence of the regulatory peptide galanin on cytokine expression in human monocytes.

Current research into neuropeptides is bringing to light many remarkable functions of these endocrine/neurocrine/paracrine factors, such as their roles in modulating immune responses. Galanin is a neuropeptide expressed in both neural and non-neural tissues and exerts its effects through three G protein-coupled receptors, GAL1,2,3 -R. It has been demonstrated that galanin has modulatory effects on immune cells, including neutrophils and natural killer cells. Because monocytes express GAL2 -R, and therefore are expected to be a target of galanin, we analyzed the effect of galanin on the expression of cytokines and chemokines by monocytes. Galanin increased the expression of IL-1ß up to 1.5-fold, TNF-α, IL-10, IL-18, and CCL3 up to twofold, and CXCL8 up to fourfold in nonactivated monocytes, but had no major effect on activated monocytes. A cross-correlation analysis of cytokine expression profiles, irrespective of the activation status of the monocytes, revealed that galanin changed the cross-correlation of the expression of certain cytokines. Galanin abolished several significant correlations in IFN-γ-stimulated monocytes. For example, treatment with 10 nM galanin changed the Spearman's rank coefficient of IL-18 and CXCL8 from 0.622 (P ≤ 0.01) to 0.126. These results further emphasize the importance of neuroregulatory peptides, such as galanin and their therapeutic potential to treat inflammatory diseases.

Galanin is a potent modulator of cytokine and chemokine expression in human macrophages.

The regulatory peptide galanin is broadly distributed in the central- and peripheral nervous systems as well as in non-neuronal tissues, where it exerts its diverse physiological functions via three G-protein-coupled receptors (GAL1-3-R). Regulatory peptides are important mediators of the cross-communication between the nervous- and immune systems and have emerged as a focus of new therapeutics for a variety of inflammatory diseases. Studies on inflammatory animal models and immune cells revealed both pro- and anti-inflammatory functions of galanin. Here, we probed specific immune-related functions of the galanin system and found galanin and GAL1-R and GAL2-R mRNA to be expressed in a range of human immune cells. In particular, macrophages displayed differentiation- and polarization-dependent expression of galanin and its receptors. Exposure to exogenous galanin affected the cytokine/chemokine expression profile of macrophages differently, depending on their differentiation and polarization, and mainly modulated the expression of chemokines (CCL2, CCL3, CCL5 and CXCL8) and anti-inflammatory cytokines (TGF-ß, IL-10 and IL-1Ra), especially in type-1 macrophages. Cytokine/chemokine expression levels in interferon-gamma- and lipopolysaccharide-polarized macrophages were upregulated whereas in unpolarized macrophages they were downregulated upon galanin treatment for 20 hours. This study illuminates the regulation of important cytokines/chemokines in macrophages by galanin, depending on specific cell activation.

An alternative mini buffy coat preparation method for adult patients with extracorporeal photopheresis contraindications.

BACKGROUND: Extracorporeal photopheresis (ECP) is an important cell-based therapy for various diseases but is limited to patients eligible for apheresis. We developed an alternative mini buffy coat (BC) preparation method using the Spectra Optia® apheresis system and compared its efficacy of white blood cell (WBC) recovery with the standard mini BC preparation method already established for pediatric patients. METHODS: Whole blood (450 ± 45 mL) samples were collected from 30 randomly selected healthy volunteer blood donors and divided into two groups. In the first group, WBCs were separated with a fully automated separator device (Compomat G4® ). In the second group, BCs were separated with the bone marrow processing program of the Spectra Optia apheresis system. RESULTS: There were no significant differences in total leukocyte counts per product between the two groups. In contrast, lymphocyte counts per product were significantly higher (P < 0.001) in BCs separated from apheresis. CONCLUSION: Our novel technique resulted in similar WBC yields but higher lymphocyte yields than the standard mini BC preparation method. This method can serve as an alternative to WBC collection in conventional ECP for adult patients with apheresis contraindications. J. Clin. Apheresis 32:12-15, 2017. © 2016 Wiley Periodicals, Inc.

The neuropeptide galanin modulates natural killer cell function.

Natural killer (NK) cells are part of the innate immune system and combat pathogens and tumors by secreting pro-inflammatory cytokines like interferon gamma (IFN-γ) and by their cytotoxic action. Galanin is a neuropeptide also expressed in peripheral tissue where it impacts several physiological functions, including inflammation. The effects of galanin are mediated via three receptors, GAL1-3. Since other neuropeptides have been shown to regulate NK cell activity, we investigated the potential of galanin to modulate human NK cell function. NK cells were isolated from human peripheral blood mononuclear cells. mRNA expression was analyzed by qRT-PCR. The dynamic mass redistribution of NK cells upon regulatory peptide stimulation was determined by label-free biochip technology. IFN-γ producing NK cells were identified by flow cytometry analysis and IFN-γ secretion was measured by ELISA. NK cell cytotoxicity was analyzed by flow cytometry via CD107a mobilization. NK cells were found to express the receptor GAL2 but not GAL1, GAL3 or galanin. Galanin per se did not affect the dynamic mass redistribution of NK cells, but significantly enhanced the response of NK cells to IL-18. Galanin significantly modulated the IFN-γ production of the CD56bright NK cell population upon IL-12 and IL-18 stimulation. Furthermore, galanin significantly modulated the IL-12 and IL-18 stimulated IFN-γ secretion. NK cell cytotoxicity was not modulated by galanin treatment. Galanin can be classified as an immunomodulatory peptide as it is able to sensitize NK cells toward specific cytokines.

Contact investigation of a case of active tuberculosis.

BACKGROUND: The Veterans Administration (VA), Marion, Illinois, following Public Health and Veterans Affairs guidance has an excellent tuberculosis (TB) control program with all employees included. METHODS: This VA is a low-risk facility for TB, according to the Centers for Disease Control and Prevention guidelines. A patient presented with active TB in January 2002. Follow-up was complicated and enlarged to the community, adjacent state, and notification of Centers for Disease Control and Prevention. The concentric circle approach in identifying highest-risk contacts had to be modified and expanded because of the immunocompromised condition of some of the contacts. RESULTS: After identification of active TB, contacts were identified. Initially 108 employees and 42 patients were reviewed for follow-up at the VA, with 98 employees and 27 patients actually tested. At 3-month follow-up there were 2 conversions. CONCLUSION: Because of excellent participation in the employee tuberculin skin testing program, conversion was readily identified among staff. Contact investigation of a case of TB requires both diligence in the program and prompt, effective communication and action between state and local health departments and hospitals.