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Stimulation of megakaryocytopoiesis in mice by human modified C-reactive protein (mCRP)
L A Potempa1, M Motie, K E Wright
1Immtech International, Evanston, IL 60201, USA.
Abstract:
The prototypic human acute phase reactant, C-reactive protein (CRP), and a structurally modified form of CRP (mCRP) were studied as agents which could stimulate thrombopoiesis in both in vitro and in vivo mouse models. mCRP, but not the widely studied (native) pentameric form of CRP, demonstrated significant megakaryocyte colony-stimulating activity. This activity was measured in plasma clot cultures incubated with pokeweed mitogen-stimulated spleen cell conditioned medium (PWM-SCM). mCRP increased the number of mouse megakaryocyte colonies in a dose-dependent manner. While significantly more colonies were observed in mCRP-treated cultures compared to controls, the kinetics of megakaryocyte growth and maturation were similar to those measured in cultures stimulated with PWM-SCM lacking mCRP. A low level of megakaryocyte growth-promoting activity was noted when mCRP was added to plasma clot cultures not incubated with spleen cell conditioned medium. However, the most striking activity of mCRP was in potentiating stimulated megakaryocyte colony formation (i.e., as a Meg-POT factor). In in vivo experiments, mCRP injected subcutaneously into normal mice resulted in significant increases in blood platelet numbers compared to control mice receiving sham injections. These results suggest that a modified form of CRP has thrombopoietic activity in both in vitro and in vivo mouse models, Therefore, one important biological role for CRP during an acute-phase response might be to contribute, after a structural modification, to the hematopoietic regulation of blood platelets.
Insights
Modified C-reactive protein (mCRP) stimulates platelet production in mice. This modified CRP form shows significant megakaryocyte-stimulating activity, suggesting a role in hematopoietic regulation during acute-phase responses.
Area of Science:
- Hematology
- Immunology
- Molecular Biology
Background:
- C-reactive protein (CRP) is a key human acute-phase reactant.
- The native pentameric form of CRP is widely studied.
- A structurally modified form of CRP (mCRP) was investigated for novel biological activities.
Purpose of the Study:
- To investigate the thrombopoietic potential of CRP and mCRP.
- To determine if CRP or mCRP can stimulate megakaryopoiesis in vitro and in vivo.
- To explore the role of mCRP in regulating blood platelet production.
Main Methods:
- In vitro studies using mouse megakaryocyte colony-stimulating assays with pokeweed mitogen-stimulated spleen cell conditioned medium (PWM-SCM).
- Dose-response experiments evaluating mCRP's effect on megakaryocyte colony formation.
- In vivo experiments involving subcutaneous injection of mCRP into normal mice to assess platelet count changes.
Main Results:
- Modified CRP (mCRP), but not native pentameric CRP, demonstrated significant megakaryocyte colony-stimulating activity in vitro.
- mCRP increased the number of mouse megakaryocyte colonies in a dose-dependent manner.
- In vivo, mCRP injection led to significant increases in blood platelet numbers in mice.
Conclusions:
- A modified form of C-reactive protein (mCRP) possesses thrombopoietic activity.
- mCRP potentiates stimulated megakaryocyte colony formation, acting as a Meg-POT factor.
- CRP, after structural modification during an acute-phase response, may contribute to the hematopoietic regulation of blood platelets.