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Hematopoietic response of splenectomized C3HeB/FeJ and C3H/HeJ mice to lipopolysaccharide
Insights
Mice with a defective LPS response gene show impaired hematopoietic stem cell activity in both spleen and marrow. This defect affects all blood-forming tissues, not just extramedullary sites.
Area of Science:
- Immunology
- Hematology
- Genetics
Background:
- Inbred mouse strains C3HeB/FeJ and C3H/HeJ exhibit differential extramedullary hematopoietic responses to lipopolysaccharide (LPS).
- C3H/HeJ mice show reduced responses in spleen-derived stem cells (CFUS) and granulocyte-macrophage colony-forming cells (GM-CFC) compared to C3HeB/FeJ mice.
Purpose of the Study:
- To investigate whether the mutational defect in C3H/HeJ mice is limited to extramedullary hematopoiesis.
- To assess the medullary hematopoietic response to LPS in splenectomized C3HeB/FeJ and C3H/HeJ mice.
Main Methods:
- Splenectomy was performed on C3HeB/FeJ and C3H/HeJ mice at 6 weeks of age.
- Mice received an intraperitoneal injection of Escherichia coli LPS-W.
- Hematopoietic response was evaluated by measuring total cells, CFUS, GM-CFC, and macrophage colony-forming cells (M-CFC) in bone marrow at 48 hours post-injection.
Main Results:
- In C3HeB/FeJ mice, LPS-W injection significantly decreased marrow-derived total cells, CFUS, GM-CFC, and M-CFC compared to controls and C3H/HeJ mice.
- The decline in C3HeB/FeJ marrow cells was followed by a rebound effect, returning to control levels.
- C3H/HeJ mice showed a characteristically nonresponsive marrow to LPS-W, with no significant variation from saline-injected controls.
Conclusions:
- The defective gene in C3H/HeJ mice impacts hematopoietic stem cell function in both medullary and extramedullary tissues.
- The LPS response defect is systemic, affecting all hematopoietic compartments that normally respond to LPS-induced factors.
Abstract:
The paired, inbred mouse strains C3HeB/FeJ and C3H/HeJ differ in their extramedullary hemopoietic response to lipopolysaccharide (LPS). The C3H/HeJ exhibit reduced responses relative to the C3HeB/FeJ in terms of colony-stimulating factor, endogenous and exogenous spleen-derived stem cells (CFUS), and spleen-derived granulocyte-macrophage colony-forming cells (GM-CFC) whereas equivocal responses were noted for the marrow-derived CFUS and GM-CFC. In an effort to determine if the mutational defect was specifically limited to extramedullary expression, we utilized C3HeB/FeJ mice and C3H/HeJ mice at 6 weeks postsplenectomy. The splenectomy emphasizes the medullary response to an i.p. injection of 10 microgram Escherichia coli, LPS-W. Significant differences were revealed in the responses of C3HeB/FeJ and C3H/HeJ marrow-derived cells. Total cells, CFUS, GM-CFC, and the macrophage colony-forming cell (M-CFC) in the C3HeB/FeJ strain all decreased significantly from their saline-injected control values as well as from their counterpart C3H/HeJ values within 48 h after injection of LPS-W. The decline in C3HeB/FeJ CFUS, GM-CFC, and M-CFC was followed by an overshoot, with subsequent return to control values. The total nucleated cells, CFUs, GM-CFC, and M-CFC derived from the C3H/HeJ marrow were characteristically nonresponsive and never varied significantly from their saline-injected control values over the observation period. These results suggest that the phenotypic effect of the defective gene can extend to all hemopoietic tissue, medullary and extramedullary, that normally respond to the factors released through expression of the LPS locus.
