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Enhancement of macrophage-mediated bactericidal activity by macrophage-mannose receptor-ligand interaction
D L Lefkowitz1, J A Lincoln, S S Lefkowitz
1Department of Biological Sciences, Texas Tech University, Lubbock 79409, USA.
Abstract:
Neutrophils represent one of the host's primary defenses against invading organisms. These cells often arrive at the site of infection prior to macrophages (M phi). Neutrophils release myeloperoxidase (MPO) into the micro-environment during phagocytosis. Previous studies by the present investigators have shown that M phi bactericidal activity is enhanced by exposure to MPO. A recent report suggests that as much as 40% of this protein is enzymatically inactive once it is released into the micro-environment. In the present study, exposure of M phi to an enzymatically inactive form of MPO (iMPO) or another mannosylated protein, mannosylated bovine serum albumin (mBSA), can induce the same enhanced Mø-mediated bacterial cell killing observed with the active form of MPO. Furthermore, this phenomenon is limited as galactosylated BSA (gBSA) did not induce enhancement of bacterial killing. The data suggest that interaction of either enzymatically active or inactive mannosylated proteins with the M phi mannose receptor (MMR), is sufficient to enhance M phi bactericidal activity and further underscores the binding of the MMR and resultant responses as a major host defense mechanism.
Insights
Inactive myeloperoxidase (MPO) and other mannosylated proteins can enhance macrophage (M phi) bacterial killing. This effect is mediated by the macrophage mannose receptor (MMR), highlighting its role in host defense.
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Background:
- Neutrophils are key immune cells arriving early at infection sites.
- Neutrophils release myeloperoxidase (MPO), which enhances macrophage (M phi) bactericidal activity.
- A significant portion of released MPO may be enzymatically inactive.
Purpose of the Study:
- To investigate if enzymatically inactive MPO or other mannosylated proteins can enhance M phi-mediated bacterial killing.
- To determine the role of the macrophage mannose receptor (MMR) in this enhanced bacterial killing.
Main Methods:
- Exposure of M phi to enzymatically inactive MPO (iMPO), mannosylated bovine serum albumin (mBSA), and galactosylated BSA (gBSA).
- Assessment of M phi-mediated bacterial cell killing.
- Analysis of the interaction with the M phi mannose receptor (MMR).
Main Results:
- Exposure to iMPO and mBSA significantly enhanced M phi bacterial killing, similar to active MPO.
- Galactosylated BSA (gBSA) did not induce enhanced bacterial killing.
- The findings suggest mannosylated proteins, active or inactive, interact with the MMR.
Conclusions:
- Mannosylated protein interaction with the MMR is sufficient to enhance M phi bactericidal activity.
- This interaction underscores the MMR's crucial role in host defense mechanisms.
- The study reveals a novel pathway for enhancing macrophage antimicrobial function.