title: Regulatory role of extracellular matrix proteins in neutrophil respiratory burst during aging.
abstract: Neutrophil respiratory burst was assessed on plates coated with fibronectin (FN) or laminin (LM), both used at dosages inhibiting polystyrene-triggered cell activation in young healthy volunteers. Under these conditions, a low, yet significant, spontaneous superoxide anion (O(2)(-)) production, matching with enhanced levels of basal adherence, was detected in FN-plated neutrophils of elderly donors. In contrast, although neutrophil stimulation with tumor necrosis factor (TNF)-alpha, granulocyte macrophage-colony stimulating factor (GM-CSF), fMLP or phorbol myristate acetate (PMA) gave rise to a massive and prolonged FN-primed O(2)(-) release, a significant impairment of oxidative response occurred in the aged group as a result of GM-CSF or fMLP cell challenge. Such an effect was not associated to an age-related imbalance of stimulant-triggered neutrophil adhesiveness to FN, even though a larger contribution of CD18-dependent versus CD18-independent pathways was observed in old as compared to young individuals. Notably, within the aged group, anti-CD18 monoclonal antibody cell pretreatment resulted in a higher suppression of FN-primed O(2)(-) release following TNF-alpha with respect to GM-CSF stimulation, thus implying that an agonist-related defect of the coupling between beta2 integrin-dependent adhesive and oxidative events is likely to occur as a feature of age. All physiological mediators failed to activate the respiratory burst of neutrophils plated on LM-coated wells in both young and aged donors. This effect appears to be the result of an active process, since neutrophils from either group of subjects adhered to LM-coated surfaces and LM inhibited in a dose-dependent manner the FN-priming effect on neutrophil O(2)(-) production. All together the findings provide additional evidence for an imbalance of neutrophil-mediated functions in the elderly.
authors.affiliation: Department of Internal Medicine, Immunology and Infectious Diseases, University of Bari Medical School, Policlinico, 70124, Bari, Italy. c.tortorella@intmed.uniba.it
authors.forename: C
authors.initials: C
authors.lastname: Tortorella
authors.forename: G
authors.initials: G
authors.lastname: Piazzolla
authors.forename: F
authors.initials: F
authors.lastname: Spaccavento
authors.forename: F
authors.initials: F
authors.lastname: Vella
authors.forename: L
authors.initials: L
authors.lastname: Pace
authors.forename: S
authors.initials: S
authors.lastname: Antonaci
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D007797:Laminin / Q000378:metabolism*; D008297:Male; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D017469:Receptors, Fibronectin / Q000378:metabolism; D016897:Respiratory Burst / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D005353:Fibronectins; D007797:Laminin; D017469:Receptors, Fibronectin; D013481:Superoxides