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Selective Harvesting of Marginating-hepatic Leukocytes
Published on: July 21, 2016
Selective Harvesting of Marginating-hepatic Leukocytes
Liat Sorski1, Lee Shaashua1, Rivka Melamed1
1Sagol School of Neuroscience & School of Psychological Sciences, Tel-Aviv University.
Abstract:
Marginating-hepatic (MH) leukocytes (leukocytes adhering to the sinusoids of the liver), were shown to exhibit unique composition and characteristics compared to leukocytes of other immune compartments. Specifically, evidence suggests a distinct pro- and anti-inflammatory profile of the MH-leukocyte population and higher cytotoxicity of liver-specific NK cells (namely, pit cells) compared to circulating or splenic immunocytes in both mice and rats. The method presented herein enables selective harvesting of MH leukocytes by forced perfusion of the liver in mice and rats. In contrast to other methods used to extract liver-leukocytes, including tissue grinding and biological degradation, this method exclusively yields leukocytes from the liver sinusoids, uncontaminated by cells from other liver compartments. In addition, the perfusion technique better preserves the integrity and the physiological milieu of MH leukocytes, sparing known physiological responses to tissue processing. As many circulating malignant cells and infected cells are detained while passing through the liver sinusoids, physically interacting with endothelial cells and resident leukocytes, the unique MH leukocyte population is strategically located to interact, identify, and react towards aberrant circulating cells. Thus, selective harvesting of MH-leukocytes and their study under various conditions may advance our understanding of the biological and clinical significance of MH leukocytes, specifically with respect to circulating aberrant cells and liver-related diseases and cancer metastases.
Insights
Researchers developed a new method to isolate liver sinusoids' unique immune cells, marginating-hepatic (MH) leukocytes. This technique preserves cell integrity, aiding research into liver diseases and cancer metastasis.
Area of Science:
- Immunology
- Hepatology
- Cell Biology
Background:
- Marginating-hepatic (MH) leukocytes, residing in liver sinusoids, possess distinct characteristics and immune profiles compared to leukocytes in other compartments.
- Liver-specific natural killer (NK) cells, or pit cells, exhibit higher cytotoxicity than circulating or splenic counterparts.
- MH leukocytes are strategically positioned to interact with and respond to circulating aberrant cells within the liver sinusoids.
Purpose of the Study:
- To present a novel method for the selective isolation of MH leukocytes from mouse and rat livers.
- To enable the study of MH leukocytes while preserving their physiological integrity and milieu.
- To advance understanding of MH leukocyte roles in liver-related diseases, cancer metastasis, and response to aberrant circulating cells.
Main Methods:
- Selective harvesting of MH leukocytes via forced liver perfusion in mice and rats.
- Comparison with traditional methods like tissue grinding and biological degradation, highlighting the superiority of perfusion.
- Preservation of MH leukocyte integrity and physiological responses, avoiding artifacts from tissue processing.
Main Results:
- The forced perfusion method yields highly pure MH leukocytes, uncontaminated by cells from other liver compartments.
- This technique preserves the physiological state of MH leukocytes, crucial for accurate functional studies.
- The isolated MH leukocytes are suitable for investigating their interactions with circulating aberrant cells.
Conclusions:
- The presented perfusion technique offers a superior method for isolating functional MH leukocytes.
- This advancement facilitates deeper research into the unique immunological functions of MH leukocytes.
- Understanding MH leukocytes is critical for developing strategies against liver diseases and metastatic cancers.
