Platelet Production In Mice Research Articles

A Comparison of Platelet Production in Mice made Thrombocytopenic by Hypoxia and by Platelet Specific Antisera

Summary. Previous experiments have shown that hypoxia causes thrombocytopenia in mice. In an attempt to define the recovery phase, mice were enclosed in hypoxia chambers for 14 d and platelet counts, total circulating platelet counts (TCPC) and masses (TCPM), platelet sizes, and %35S incorporation into platelets were determined over the next 8 d while the mice were kept at ambient O2 levels. For comparison, untreated mice and mice made thrombocytopenic by injection of rabbit anti‐mouse‐platelet serum (RAMPS) were used. Both 14 d of hypoxia and RAMPS treatment resulted in severe thrombocytopenia. TCPC and TCPM were similar in both exhypoxic and RAMPS‐injected mice. However, the platelet count recovery pattern of exhypoxic‐thrombocytopenic mice did not show the rebound‐thrombocytosis which was characteristic of RAMPS‐induced thrombocytopenia, apparently because of dilution of platelets by increased blood volumes. Average platelet sizes were larger than normal 2 d posthypoxia or after RAMPS‐treatment, followed by a decline toward normal; platelets from exhypoxic mice, however, remained larger. Per cent 35S incorporation into platelets was lower in exhypoxic mice than in RAMPS‐treated mice; lower numbers of megakaryocytes were observed immediately after removal from hypoxia followed by an increase in number and size by 2 d later. Also, thrombopoietin was detected in plasma of RAMPS‐treated mice, but not in plasma of exhypoxic‐thrombocytopenic mice. Therefore, it seems possible that hypoxia reduced the numbers of megakaryocytes, resulting in depressed thrombocytopoiesis of mice at the time of removal from hypoxic atmospheres.

Neutralizing Antiserum to Thrombopoietin

SummaryPotent thrombopoietin (TSF) materials were mixed with normal rabbit serum and serum from rabbits that had been immunized with TSF-rich fractions of human plasma, human urine, or kidney cell culture media; the supernatant fluids from these incubations were then assayed for TSF content by means of the immunothrombocythemic mouse assay. The results indicate that TSF, after incubation with normal rabbit serum, stimulated platelet production in mice, whereas pretreatment of the TSF with anti-TSF serum neutralized the ability of TSF to stimulate thrombocytopoiesis in mice. These data support the hypothesis that TSF found in kidney cell culture medium is immunologically similar to TSF from human urine or plasma.

Effect of vincristine on platelet production in mice.

SummaryPlatelet production was investigated using [75Se]selenomethionine bio‐assay in C57BL mice after a single injection of vincristine within the dose range 0.2–3.2 mg/kg. The changes in the circulating platelet count were also followed. There was an immediate, not strictly dose‐dependent, fall in the number of platelets, a quick recovery with an overshoot after small doses, delayed recovery with a moderate overshoot after intermediate doses and a slow recovery returning to normal levels after large doses. The drug caused an overproduction of platelets with every dose used, but this was not necessarily reflected in the peripheral platelet count. It seems unlikely, at least after the smaller doses, that the early fall in platelets plays a role in the increased platelet production. Platelet precursors are resistant to a single dose of vincristine and the drug may have a primary stimulatory effect on the megakaryocytopoietic system.