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Normal unstimulated lymphocytes produce granulopoietic inhibitory activity
A E Irvine1, M A French, J M Bridges
1Department of Haematology, Queen's University of Belfast, Northern Ireland.
Insights
Normal lymphocytes inhibit bone marrow colony formation through a novel molecular mechanism. This granulopoietic inhibitory activity (GIA) is a large glycoprotein, not related to known cytokines or isoferritins.
Area of Science:
- Hematology
- Immunology
- Molecular Biology
Background:
- Normal lymphocytes can inhibit the formation of bone marrow colonies.
- The molecular basis for this inhibitory phenomenon requires further characterization.
Purpose of the Study:
- To identify the molecular nature of the granulopoietic inhibitory activity (GIA) produced by lymphocytes.
- To differentiate GIA from known inhibitory factors like interferons and tumor necrosis factor.
Main Methods:
- Coculture of lymphocytes with bone marrow.
- Specific assays to test for known inhibitory factors.
- Neutralizing monoclonal antibodies.
- Biochemical characterization including molecular weight determination.
- Cell cycle analysis to determine target phase.
Main Results:
- Granulopoietic inhibitory activity (GIA) was confirmed to have a molecular basis.
- GIA is not mediated by alpha-interferon, gamma-interferon, tumor necrosis factor, or isoferritins.
- Biochemical analysis indicates GIA is a glycoprotein with a molecular weight >100,000 daltons.
- GIA appears to target cells in the S phase of the cell cycle, though not exclusively.
Conclusions:
- Lymphocyte-mediated inhibition of granulopoiesis involves a novel molecular entity, GIA.
- GIA is a large glycoprotein distinct from previously identified hematopoietic inhibitors.
- Further research into GIA's mechanism of action and biological role is warranted.
Abstract:
Normal unstimulated lymphocytes cocultured with normal bone marrow will inhibit day-7 colony- forming units in culture. We have shown that this phenomenon has a molecular basis and attempted to characterize it further. Using specific assays and neutralizing monoclonal antibodies we have found that this granulopoietic inhibitory activity (GIA) is not due to alpha- or gamma-interferon, tumor necrosis factor, or acidic or basic isoferritins. Biochemical studies suggest that it is a glycoprotein with a molecular weight greater than 100,000 daltons. It appears to act on cells in S phase, although it may not be S-phase specific. GIA represents a novel inhibitor that merits further investigation.