title: Regulation of Neutrophil Degranulation and Cytokine Secretion: A Novel Model Approach Based on Linear Fitting.
abstract: Neutrophils participate in the maintenance of host integrity by releasing various cytotoxic proteins during degranulation. Due to recent advances, a major role has been attributed to neutrophil-derived cytokine secretion in the initiation, exacerbation, and resolution of inflammatory responses. Because the release of neutrophil-derived products orchestrates the action of other immune cells at the infection site and, thus, can contribute to the development of chronic inflammatory diseases, we aimed to investigate in more detail the spatiotemporal regulation of neutrophil-mediated release mechanisms of proinflammatory mediators. Purified human neutrophils were stimulated for different time points with lipopolysaccharide. Cells and supernatants were analyzed by flow cytometry techniques and used to establish secretion profiles of granules and cytokines. To analyze the link between cytokine release and degranulation time series, we propose an original strategy based on linear fitting, which may be used as a guideline, to (i) define the relationship of granule proteins and cytokines secreted to the inflammatory site and (ii) investigate the spatial regulation of neutrophil cytokine release. The model approach presented here aims to predict the correlation between neutrophil-derived cytokine secretion and degranulation and may easily be extrapolated to investigate the relationship between other types of time series of functional processes.
authors.affiliation: Calcium Signalling and Inflammation, Life Sciences Research Unit, University of Luxembourg, 162A Avenue de la Faïencerie, 1511 Luxembourg, Luxembourg.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Naegelen
authors.affiliation: Calcium Signalling and Inflammation, Life Sciences Research Unit, University of Luxembourg, 162A Avenue de la Faïencerie, 1511 Luxembourg, Luxembourg.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Beaume
authors.affiliation: Calcium Signalling and Inflammation, Life Sciences Research Unit, University of Luxembourg, 162A Avenue de la Faïencerie, 1511 Luxembourg, Luxembourg.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Plançon
authors.affiliation: Calcium Signalling and Inflammation, Life Sciences Research Unit, University of Luxembourg, 162A Avenue de la Faïencerie, 1511 Luxembourg, Luxembourg.
authors.forename: Véronique
authors.initials: V
authors.lastname: Schenten
authors.affiliation: Calcium Signalling and Inflammation, Life Sciences Research Unit, University of Luxembourg, 162A Avenue de la Faïencerie, 1511 Luxembourg, Luxembourg.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Tschirhart
authors.affiliation: Calcium Signalling and Inflammation, Life Sciences Research Unit, University of Luxembourg, 162A Avenue de la Faïencerie, 1511 Luxembourg, Luxembourg.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Bréchard
mesh_terms: D000954:Antigens, Surface / Q000378:metabolism; D015550:Cell Degranulation / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008954:Models, Biological; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism*; D010641:Phenotype; D013997:Time Factors
chemical_list: D000954:Antigens, Surface; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides