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Updated: Sep 29, 2026
Assessing Anti-fungal Activity of Isolated Alveolar Macrophages by Confocal Microscopy
Published on: July 9, 2014
Pulmonary surfactant protein A up-regulates activity of the mannose receptor, a pattern recognition receptor
Alison A Beharka1, Cecilia D Gaynor, Byoung K Kang
1Veterans Affairs Medical Center and Division of Infectious Diseases, Department of Medicine and Microbiology, Interdisciplinary Immunology Program, University of Iowa, Iowa City, IA 52242, USA. hiroyuki.matsue@utsouthwestern.edu
Abstract:
Inhaled particulates and microbes are continually cleared by a complex array of lung innate immune determinants, including alveolar macrophages (AMs). AMs are unique cells with an enhanced capacity for phagocytosis that is due, in part, to increased activity of the macrophage mannose receptor (MR), a pattern recognition receptor for various microorganisms. The local factors that "shape" AM function are not well understood. Surfactant protein A (SP-A), a major component of lung surfactant, participates in the innate immune response and can enhance phagocytosis. Here we show that SP-A selectively enhances MR expression on human monocyte-derived macrophages, a process involving both the attached sugars and collagen-like domain of SP-A. The newly expressed MR is functional. Monocyte-derived macrophages on an SP-A substrate demonstrated enhanced pinocytosis of mannose BSA and phagocytosis of Mycobacterium tuberculosis lipoarabinomannan-coated microspheres. The newly expressed MR likely came from intracellular pools because: 1) up-regulation of the MR by SP-A occurred by 1 h, 2) new protein synthesis was not necessary for MR up-regulation, and 3) pinocytosis of mannose BSA via MR recycling was increased. AMs from SP-A(-/-) mice have reduced MR expression relative to SP-A(+/+). SP-A up-regulation of MR activity provides a mechanism for enhanced phagocytosis of microbes by AMs, thereby enhancing lung host defense against extracellular pathogens or, paradoxically, enhancing the potential for intracellular pathogens to enter their intracellular niche. SP-A contributes to the alternative activation state of the AM in the lung.
Insights
Surfactant protein A (SP-A) enhances macrophage mannose receptor (MR) expression, boosting phagocytosis. This mechanism improves lung immune defense against microbes.
Area of Science:
- Pulmonary immunology
- Innate immune responses
- Macrophage biology
Background:
- Alveolar macrophages (AMs) clear inhaled particles and microbes via phagocytosis.
- Macrophage mannose receptor (MR) is crucial for recognizing and engulfing microorganisms.
- Local factors influencing AM function, particularly SP-A, are not fully understood.
Purpose of the Study:
- To investigate the role of surfactant protein A (SP-A) in regulating macrophage mannose receptor (MR) expression and function.
- To elucidate the mechanism by which SP-A influences MR expression on macrophages.
- To determine the impact of SP-A-mediated MR up-regulation on phagocytosis and lung host defense.
Main Methods:
- Treatment of human monocyte-derived macrophages with SP-A.
- Assessment of MR expression using flow cytometry and functional assays.
- Investigation of SP-A's structural domains involved in MR up-regulation.
- Analysis of AMs from SP-A knockout mice.
Main Results:
- SP-A selectively enhances MR expression on human monocyte-derived macrophages.
- SP-A's sugar and collagen-like domains are involved in MR up-regulation.
- Newly expressed MR is functional, enhancing pinocytosis and phagocytosis.
- MR up-regulation by SP-A occurs rapidly and independently of new protein synthesis, suggesting intracellular pools.
- AMs from SP-A knockout mice exhibit reduced MR expression.
Conclusions:
- SP-A up-regulates functional MR expression on macrophages, enhancing phagocytic capacity.
- This SP-A-mediated mechanism contributes to lung host defense against pathogens.
- SP-A plays a role in the alternative activation state of alveolar macrophages.
- SP-A influences both the clearance of extracellular pathogens and the entry of intracellular pathogens.
