Neutrophil secretion products regulate anti-bacterial activity in monocytes and macrophages

Abstract

SummaryMacrophages represent a multi-functional cell type in innate immunity that contributes to bacterial clearance by recognition, phagocytosis and killing. In acute inflammation, infiltrating neutrophils release a wide array of preformed granule proteins which interfere functionally with their environment. Here, we present a novel role for neutrophil-derived granule proteins in the antimicrobial activity of macrophages. Neutrophil secretion obtained by antibody cross-linking of the integrin subunit CD18 (X-link secretion) or by treatment with N-Formyl-Met-Leu-Phe (fMLP secretion) induced a several-fold increase in bacterial phagocytosis by monocytes and macrophages. This response was associated with a rapid activation of the monocytes and macrophages as depicted by an increase in cytosolic free Ca 2+ . Interestingly, fMLP secretion had a more pronounced effect on monocytes than the X-link secretion, while the opposite was observed for macrophages. In addition, polymorphonuclear cells (PMN) secretion caused a strong enhancement of intracellular reactive oxygen species (ROS) formation compared to incubation with bacteria. Thus, secretion of neutrophil granule proteins activates macrophages to increase the phagocytosis of bacteria and to enhance intracellular ROS formation, indicating pronounced intracellular bacterial killing. Both mechanisms attribute novel microbicidal properties to PMN granule proteins, suggesting their potential use in anti-microbial therapy.

Neutrophil-derived azurocidin alarms the immune system

“…In this study, PMN-derived azurocidin activates macrophages via ␤ 2 -integrins, which causes release of TNF-␣ and IFN-␥ [44,52]. As a consequence, CD64 and CD32 are up-regulated.…”

The novel polysaccharide deacetylase homologue Pdi contributes to virulence of the aquatic pathogen Streptococcus iniae

“…Reactive oxygen species and AMPs are mechanisms used by phagocytes and other immune cell types to mediate clearance of bacterial invaders in whole blood (Gallo & Nizet, 2003;Locke et al, 2007a;Soehnlein et al, 2008). To further analyse why the Dpdi mutant was less able to survive in whole fish blood, we compared the resistance of WT and the Dpdi mutant to oxidative killing by hydrogen peroxide, as well as the sensitivities of both strains to the HSB-derived AMP moronecidin or the bacterially derived cationic AMP polymyxin B.…”

Effect of the total crude extracts of Hibiscus sabdariffa on the immune system in the Wistar albino rats

“…The increased adhesion of the neutrophils to nylon fibers could be due to the compounds in the herb that may improve the migration of phagocytes such as neutrophils to the foreign body in blood vessels (Guyton and Hall, 2006;Srikumar et al, 2007). The neutrophils represent a multifunctional cell type in innate immunity that contributes to bacterial clearance by recognition, phagocytosis and killing of foreign bodies (Guyton and Hall, 2006;Srikumar et al, 2007), whereas the T and Blymphocytes are involved and responsible for production of antibodies leading to enhancement of immunity (Guyton and Hall, 2006;Srikumar et al, 2007;GarlandScience, 2008;Soehnlein et al, 2008). The observed increase in the footpad thickness of the Wistar albino rats which is a measure of the DTH as a result of the challenge of the SRBC antigens could be due to some of the compounds found in the herbal extract.…”