Mechanisms of splenic control of murine malaria: tissue culture studies of the erythropoietic interplay of spleen, bone marrow, and blood in lethal (strain 17XL) Plasmodium yoelii malaria in BALB/c mice.
This work characterizes the erythropoietic interplay of the spleen, blood, and bone marrow in a lethal murine malaria, strain 17XL P. yoelii. This malaria runs a fulminant 7 day course in BALB/c/ByJ mice, marked by high levels of parasitized reticulocytes with death likely due to anemia. We have quantitated the levels of burst forming units-erythroid (BFU-E), the early, niche-seeking, largely erythropoietin-unresponsive erythropoietic precursors, and of colony forming units-erythroid (CFU-E), the more differentiated sessile erythropoietin-responsive precursors, in bone marrow, blood, and spleen, through the course of this malaria. A decline in marrow BFU-E began on day 2, but recovered, relatively, after day 3. Marrow cellularity declined, being but 75% normal on day 6. Spleen weight increased about 5-fold within 6 days with enlargement of erythroid, lymphoid, macrophage, and stromal compartments. Splenic BFU-E increased in the first 24 hr and 5-fold by day 6. Splenic CFU-E increased in the first 24 hr and into day 4. They then declined and showed a secondary, large-scale, sustained rise interrupted by death. Because the spleen was enlarging, a greater than 60-fold increase in the absolute number of splenic CFU-E occurred at the time of death. Marrow CFU-E followed the same pattern as splenic CFU-E, but the terminal increase represented but a 4-fold absolute increase because of declining marrow cellularity. High levels of erythropoietin occurred only late in the course of disease, likely in response to profound anemia.(ABSTRACT TRUNCATED AT 250 WORDS)
School of Veterinary Medicine, University of Pennsylvania, Philadelphia.
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L
Weiss
J
J
Johnson
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W
Weidanz
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology*; D003114:Colony-Forming Units Assay; D046508:Culture Techniques; D004912:Erythrocytes / Q000187:drug effects / Q000473:pathology*; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000097:blood / Q000494:pharmacology; D006411:Hematopoiesis, Extramedullary / Q000187:drug effects; D008288:Malaria / Q000097:blood / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010967:Plasmodium yoelii; D013154:Spleen / Q000187:drug effects / Q000473:pathology*; D013268:Stimulation, Chemical; D013997:Time Factors
D004921:Erythropoietin