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Megakaryocyte progenitors in paroxysmal nocturnal haemoglobinuria are sensitive to complement
N Basara1, P Antunovic, D Sefer
1Institute of Haematology, Clinical Center of Serbia, Belgrade, Yugoslavia.
Abstract:
We have investigated growth in vitro of bone marrow megakaryocytic progenitors (CFU-Mk) in 7 patients with paroxysmal nocturnal haemoglobinuria (PNH) to determine the sensitivity of CFU-Mk to complement. Bone marrow light density mononuclear cells were exposed to fresh or heat-inactivated AB human serum in the presence of medium or isotonic sucrose solution. We found that the proliferative activity of bone marrow CFU-Mk in PNH patients was significantly lower than in controls. In addition, the number of CFU-Mk in PNH bone marrow cells exposed to isotonic sucrose and complement was reduced to 25% of that in PNH cells exposed to isotonic sucrose without complement. In conclusion, our finding showed an increased sensitivity of CFU-Mk in PNH bone marrow cells to complement, supporting the hypothesis that the PNH defect is present at the level of CFU-Mk.
Insights
Bone marrow megakaryocytic progenitors (CFU-Mk) from paroxysmal nocturnal hemoglobinuria (PNH) patients show increased sensitivity to complement. This finding supports the PNH defect being present at the CFU-Mk level.
Area of Science:
- Hematology
- Immunology
- Cell Biology
Background:
- Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired blood disorder.
- The PNH defect is thought to involve complement-mediated damage to blood cells.
- Megakaryocytic progenitors (CFU-Mk) are crucial for platelet production.
Purpose of the Study:
- To investigate the sensitivity of CFU-Mk to complement in PNH patients.
- To determine if the PNH defect affects CFU-Mk growth and survival.
Main Methods:
- Bone marrow mononuclear cells from 7 PNH patients and controls were cultured in vitro.
- Cells were exposed to fresh or heat-inactivated human serum (complement source).
- Proliferative activity of CFU-Mk was assessed under different conditions.
Main Results:
- CFU-Mk proliferative activity was significantly lower in PNH patients compared to controls.
- Exposure to complement reduced CFU-Mk numbers by 75% in PNH samples.
- PNH CFU-Mk demonstrated heightened sensitivity to complement-mediated damage.
Conclusions:
- CFU-Mk in PNH patients exhibit increased sensitivity to complement.
- This heightened sensitivity supports the hypothesis that the PNH defect originates at the CFU-Mk level.
- Findings suggest complement-mediated destruction of PNH CFU-Mk contributes to the disease pathology.