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A discrete subpopulation of human monocytes expresses a neutrophil-like proinflammatory (P) phenotype
C A Owen1, M A Campbell, S S Boukedes
1Department of Medicine, University of Utah Health Sciences Center, Salt Lake City 84132.
Abstract:
We have demonstrated that a discrete and naturally occurring subpopulation of human monocytes expresses a neutrophil-like proinflammatory (P) phenotype. P monocytes constitute 20-30% of the circulating monocyte pool and are characterized by 1) avid adherence to extracellular matrix through high-level cell-surface expression of alpha 5-, beta 1-, and beta 2-integrins; 2) high capacity to produce reactive oxygen species; 3) high content of serine proteinases and alpha 1-proteinase inhibitor; and 4) proteolytic activity against a soluble peptide human leukocyte elastase substrate, [3H]elastin, and solid-phase fibronectin, even in the presence of proteinase inhibitors. However, P monocytes express little or no cell-surface HLA-DR antigen, suggesting that they are unable to participate in specific immune responses. In contrast, the remainder of circulating monocytes have a low proinflammatory potential but contain the population of monocytes with high-level expression of HLA-DR antigen. P monocytes can readily be separated from the remainder of monocytes on the basis of 1) their capacity to adhere to fibronectin; and 2) their absent expression of HLA-DR antigen when flow cytometry or immunomagnetic beads are used. Our data indicate that, when recruited to sites of inflammation, P monocytes can either promote resolution of inflammation or contribute to tissue injury.
Insights
A distinct human monocyte subpopulation exhibits neutrophil-like inflammatory properties, characterized by strong adherence and protease activity but lacking immune response markers. These P monocytes can influence inflammation resolution or tissue damage.
Area of Science:
- Immunology
- Cell Biology
Background:
- Monocytes are key immune cells with diverse functions.
- Existing knowledge lacks detailed characterization of distinct monocyte subpopulations.
Purpose of the Study:
- To identify and characterize a neutrophil-like proinflammatory monocyte subpopulation.
- To understand the functional implications of this monocyte phenotype.
Main Methods:
- Flow cytometry and immunomagnetic bead separation.
- Assays for extracellular matrix adherence, reactive oxygen species production, and protease activity.
- Analysis of HLA-DR antigen expression.
Main Results:
- A subpopulation of human monocytes (P monocytes) displays neutrophil-like proinflammatory characteristics.
- P monocytes exhibit avid adherence, high reactive oxygen species production, and significant proteolytic activity.
- These monocytes express low or absent HLA-DR antigen, limiting their role in specific immune responses.
- P monocytes can be separated based on fibronectin adherence and HLA-DR expression.
Conclusions:
- P monocytes represent a distinct functional subset within the circulating monocyte pool.
- Their phenotype suggests a dual role in inflammation: promoting resolution or contributing to tissue injury.
- Understanding P monocytes is crucial for modulating inflammatory responses.