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HemaCare Macrophages Help Solve Mysteries of Immune Regulation

Jan 26, 2021 10:25:00 AM / by Nancy Andon, MSc

AdobeStock_98515861-1_field of cells, macrophages attack the cells, viruses attack the cells, action of the human immune systemThe use of HemaCare-sourced macrophages has been cited in a recent publication in the Journal of Immunology. The paper is a collaboration between the University of Maryland in College Park, and biopharmaceutical company AstraZeneca. [1]

The role of macrophages in the human immune system is not nearly as well-known as T cells or B cells, which are seemingly ubiquitous in the cell and gene therapy field. Like lymphocytes, macrophages are derived from hematopoietic stem cells. Unlike the lymphoid lineage, however, myeloid precursors ultimately produce in the macrophage an immune cell capable of both antigen presentation and phagocytic activity.

Macrophages are found in all body tissues, making them a compelling target for cell therapy. Unfortunately, the cells are largely underutilized because so little is known about how their activation state is controlled and how they help regulate the immune system.

The Maryland research team hypothesized that if they could learn to manipulate macrophages’ activation state, scientists would have a much better chance of designing effective treatments for inflammatory and proliferative diseases.

The team sourced their macrophages from HemaCare, which has supplied cellular starting materials for several well-known FDA-approved cancer immunotherapies. Their first goal was to identify signaling pathways that led to changes in macrophage characteristics and function. They planned to use the results to identify promising targets that could allow them to manipulate the cell’s immune response.

Building on prior research done using mouse macrophage immune complexes (IC), the authors determined that human macrophages respond to a similar IC, which they named R-Mf-IC. The group used a high-throughput sequencing technique to characterize the human macrophages generated in response to inflammatory stimulants.

The authors compared resting macrophages to macrophages stimulated with either LPS (a general immune cell agonist) or LPS plus R-Mf-IC. Results revealed that macrophages stimulated with LPS plus R-Mf-IC responded by upregulating genes known to be involved in suppressing inflammation, as well as genes involved in promoting tissue remodeling, angiogenesis, and immune regulation.

The research group went on to see if they could use their findings to identify biomarkers for macrophages in various activation states. They also wanted to confirm the presence of R-Mf-IC in human tissue. Using flow cytometry, the authors showed that R-Mf-IC-induced macrophages upregulate several biologically important proteins, including DC-STAMP, a cell surface protein also expressed on dendritic cells. To look for R-Mf-IC-activated macrophages in human tissue, the scientists used lesion-derived tissue from patients infected with leprosy, a disease that has long been associated with an inadequate immune response. They found that macrophages in this tissue had high DC-STAMP expression, a possible sign that overproduction of regulatory macrophages could be driving the immune system’s failure to adequately protect its host.

The data in this publication constitutes a ground-breaking characterization of human macrophages. The demonstrated capacity to generate macrophages with an anti-inflammatory, pro-healing phenotype provides important insight into disease pathology. It has enormous potential for the treatment of cancer, infectious and inflammatory diseases.

Reference

  1. Dalby E., et al. Immune Complex-Driven Generation of Human Macrophages with Anti-Inflammatory and Growth-Promoting Activity. J Immunol. May 2020.

Topics: Cancer, Macrophages, Immunotherapy (Immunology)

Nancy Andon, MSc

Written by Nancy Andon, MSc

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