Thrombospondins deployed by thrombopoietic cells determine angiogenic switch and extent of revascularization
J. Clin. Invest. Hans-Georg Kopp, et al. 116:3277 doi:10.1172/JCI29314 [
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Figure 3TSP deficiency enhances megakaryocyte repopulation of the bone marrow and platelet production after myelosuppression. (
A) After 250 mg/kg of 5-FU treatment, WT mice experienced pancytopenia followed by rebound thrombocytosis. Platelets reverted to normal around day 24.
TSP-DKO mice displayed a more rapid regeneration, with 8.9 × 10
5 platelets/μl compared with 4.77 × 10
5 platelets/μl in WT animals on day 7. Furthermore, rebound thrombocytosis was exaggerated, with platelets reaching 5.5 × 10
6/μl compared with 2.9 × 10
6/μl in WT controls on day 14 (
n = 6,
P = 0.006). *
P < 0.05. (
B) Leukocytes and (
C) hemoglobin concentrations did not show significant differences between
TSP-DKO and WT mice (
n = 6). (
D)
TSP-DKO mice had higher numbers of megakaryocytes at all time points following 5-FU injection (
P < 0.05). While megakaryocytes reached their lowest levels on day 7 in WT mice, megakaryocyte concentration returned to normal levels in
TSP-DKO mice on day 7 (
P < 0.0003). (
E) After 5-FU injection, endothelial cell mass plummeted to about 2% of hematopoietic marrow surface area and reverted to normal around day 14. In
TSP-DKO mice, the overall course of these changes was similar to that in WT mice. However, MECA32-positive surface area never decreased to less than 4.9% (day 7 after 5-FU injection;
P < 0.005). (
F and
G) The same femoral marrow as represented in
E stained with H&E (
F) and anti-citrulline antibody (
G). DAB was counterstained with hematoxylin.
TSP-DKO marrow showed extreme megakaryocytosis at day 10 after 5-FU injection. Green arrows indicate megakaryocytes. Original magnification, ×400.
