Neonatal Neutrophils with Prolonged Survival Secrete Mediators Associated with Chronic Inflammation

Abstract

Background: The resolution of inflammation involves the efficient removal of apoptotic neutrophils (PMN). However, a subpopulation of PMN that are resistant to apoptosis may contribute to PMN persistence in tissues, an early hallmark of chronic inflammation. We previously made observations that neonatal PMN with prolonged survival had augmented expression of CD18/CD11b, an adhesion molecule critical to inflammation. Objectives: The objectives of this study were to test the hypothesis that surviving neonatal PMN retain the capacity to secrete key mediators associated with chronic inflammation. Methods: We profiled cytokine and chemokine secretion patterns of lipopolysaccharide (LPS)-stimulated neonatal and adult PMN using multicytokine array and ELISA. Results: We observed that surviving 24-hour neonatal PMN stimulated with LPS had enhanced secretion of interleukin (IL)-8, a chemokine involved in PMN activation and recruitment. In addition, 24-hour neonatal PMN secreted levels of monocyte inhibitory protein (MIP)-1β that were higher than those secreted by 0-hour PMN, but amounts of IL-1 receptor antagonist (IL-1Ra) were lower. Conclusions: The results of the present study extend previous observations of augmented function in surviving neonatal neutrophils, and further suggest their potential contribution to the pathogenesis of inflammatory disorders in neonates.

Moringa Tea Blocks Acute Lung Inflammation Induced by Swine Confinement Dust Through a Mechanism Involving TNF-α Expression, C-Jun N-Terminal Kinase Activation and Neutrophil Regulation

“…IL-1Ra is an antagonist to IL-1α/β signaling in the lung (Wilmott et al, 1998). It is produced at high levels by neutrophils in response to LPS stimulation or exposure to TNF-α (McColl et al, 1992;Nguyen et al, 2010) and in a guinea pig model of late asthmatic reactions (Okada et al, 1995). Ning and colleagues investigated mice with acute lung inflammation and reported a positive correlation in expression pattern between TREM-1 and TNF-α whereby both increased with LPS treatment (Liu et al, 2010).…”

Toll-Like Receptor 1/2 Stimulation Induces Elevated Interleukin-8 Secretion in Polymorphonuclear Leukocytes Isolated from Preterm and Term Newborn Infants

“…They also play an important role in tissue re- pair and integration of the innate and adaptive immune responses [1] . If, however, these specialized, defensive responses to tissue damage or infection become dysregulated, PMNs may paradoxically become agents of inflammatory tissue injury [1,[5][6][7][8][9][10] .…”

MSCS in Scenarios of Infection and Inflammation: Focus on Neonatal Diseases

“…Under physiological conditions, apoptosis of activated monocytes and neutrophils [1] and polarization of macrophages from a proinflammatory M1 phenotype towards an anti-inflammatory M2 phenotype prevent the hyper-responsiveness of the innate immunity [22]. Cord blood-derived monocytes and neutrophils appear to be more resistant to apoptosis than adult peripheral blood-derived cells [23,24]. The surviving neutrophils contribute to sustained inflammation through the secretion of particularly high levels of pro-inflammatory cytokines after LPS stimulation in vitro [23].…”

“…Cord blood-derived monocytes and neutrophils appear to be more resistant to apoptosis than adult peripheral blood-derived cells [23,24]. The surviving neutrophils contribute to sustained inflammation through the secretion of particularly high levels of pro-inflammatory cytokines after LPS stimulation in vitro [23]. Moreover, immaturity of Toll-like receptor signaling is associated with a pronounced inflammatory response in neonatal immune cells [25].…”