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Neutrophil secretion products regulate anti-bacterial activity in monocytes and macrophages
O Soehnlein1, E Kenne, P Rotzius
1Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden. oliver.sohnlein@ki.se
Abstract:
Macrophages 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 anti-microbial 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.
Insights
Neutrophil granule proteins enhance macrophage antimicrobial activity by increasing bacterial phagocytosis and reactive oxygen species (ROS) production. These findings reveal novel microbicidal roles for neutrophil proteins, suggesting potential anti-microbial therapy applications.
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Background:
- Macrophages are key innate immune cells for bacterial clearance.
- Neutrophils release granule proteins during acute inflammation.
- The role of neutrophil granule proteins in macrophage antimicrobial activity is not well understood.
Purpose of the Study:
- To investigate the novel role of neutrophil-derived granule proteins in enhancing macrophage anti-microbial functions.
- To determine the effects of neutrophil secretion on bacterial phagocytosis and intracellular killing by monocytes and macrophages.
Main Methods:
- Stimulation of neutrophils to induce secretion (antibody cross-linking of CD18 or fMLP treatment).
- Incubation of monocytes and macrophages with neutrophil secretions.
- Measurement of bacterial phagocytosis, intracellular calcium (Ca2+) levels, and reactive oxygen species (ROS) formation.
Main Results:
- Neutrophil secretions significantly increased bacterial phagocytosis by monocytes and macrophages.
- Secretions induced rapid monocyte and macrophage activation, evidenced by increased cytosolic free Ca2+.
- Polymorphonuclear cell (PMN) secretions enhanced intracellular ROS formation, indicating increased bacterial killing.
Conclusions:
- Neutrophil granule proteins activate macrophages, enhancing their capacity for bacterial phagocytosis and ROS production.
- These findings suggest novel microbicidal properties of PMN granule proteins.
- Neutrophil granule proteins show potential for development into anti-microbial therapies.
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