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Published on: September 9, 2014
Lipopolysaccharide interference in erythropoiesis in mice
P Brendt1, I Rehfeld2, A Kamphausen3
1Staff Anaesthesiologist.
Abstract:
Anaemia is a common problem in septic patients. We tested whether lipopolysaccharide suppressed erythropoiesis and interfered with erythropoietin. Male mice (strain C57BL/6, n = 76) were injected Escherichia coli lipopolysaccharide (serotype O127:B8; 20 mg.kg(-1) intraperitoneally) or vehicle, followed by either erythropoietin (5000 IU.kg(-1) intraperitoneally) or vehicle, and killed after 24 or 72 h. Femur bone marrow cells were stained for Ter-119, CD71 and C-Kit antigen using specific flow cytometry gates for proerythroblasts, basophilic, polychromatic and orthochromatic erythroblasts, and peripheral blood reticulocytes were counted. Erythropoietin stimulated erythropoiesis, as evidenced by increased reticulocytes after 72 h by 197% and proerythroblasts by 50% (p < 0.05). Lipopolysaccharide alone decreased proerythroblasts by 53% and basophilic erythroblasts by 75% (p < 0.05). Orthochromatic erythroblasts doubled after lipopolysaccharide exposure (p < 0.05) without any increase in reticulocytes. Lipopolysaccharide completely suppressed erythropoietin's stimulatory effects and evoked a maturation block at the late stage of erythropoiesis. Lipopolysaccharide could cause anaemia in sepsis.
Insights
Lipopolysaccharide, a component of E. coli, impairs red blood cell production (erythropoiesis) and blocks the effects of erythropoietin. This suggests lipopolysaccharide may cause anemia in sepsis patients.
Area of Science:
- Hematology
- Immunology
- Pathophysiology
Background:
- Anemia is a frequent complication in sepsis patients.
- The impact of lipopolysaccharide (LPS) on erythropoiesis and erythropoietin signaling in sepsis is not fully understood.
Purpose of the Study:
- To investigate whether lipopolysaccharide suppresses erythropoiesis and interferes with erythropoietin's function.
- To elucidate the effects of lipopolysaccharide on red blood cell development during sepsis.
Main Methods:
- Male C57BL/6 mice were administered lipopolysaccharide (LPS) or vehicle, followed by erythropoietin or vehicle.
- Flow cytometry was used to analyze erythropoiesis markers (Ter-119, CD71, C-Kit) in bone marrow.
- Peripheral blood reticulocyte counts were assessed at 24 and 72 hours post-injection.
Main Results:
- Erythropoietin significantly increased reticulocytes and proerythroblasts, confirming its stimulatory effect on erythropoiesis.
- Lipopolysaccharide alone reduced proerythroblasts and basophilic erythroblasts but increased orthochromatic erythroblasts, indicating a late-stage maturation block.
- Lipopolysaccharide completely abolished erythropoietin's positive effects on erythropoiesis and prevented reticulocyte production.
Conclusions:
- Lipopolysaccharide significantly impairs erythropoiesis by blocking red blood cell maturation.
- Lipopolysaccharide interferes with erythropoietin signaling, negating its therapeutic effects.
- These findings suggest lipopolysaccharide is a contributing factor to anemia in sepsis.
