Regulatory role of extracellular matrix proteins in neutrophil respiratory burst during aging.

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.