Bidirectional effect of interleukin-10 on early murine B-cell development: stimulation of flt3-ligand plus interleukin-7-dependent generation of CD19(-) ProB cells from uncommitted bone marrow progenitor cells and growth inhibition of CD19(+) ProB cells.

B-cell commitment and early development from multipotent hematopoietic progenitor cells has until recently been considered to be dependent on direct interaction with stromal cells. We recently showed that the flt3 ligand (FL) has a unique ability to interact with interleukin-7 (IL-7) to directly and selectively promote B-cell development from murine bone marrow progenitor cells with a combined myeloid and lymphoid potential. Here we report that whereas IL-10 alone has no ability to stimulate growth of primitive (Lin-Sca-1(+)c-kit+) bone marrow progenitor cells, it potently enhances FL + IL-7-induced proliferation (sevenfold). This enhanced proliferation results from recruitment of progenitors unresponsive to FL + IL-7 alone, as well as from increased growth of individual clones, resulting in a 7,000-fold cellular expansion over 12 days. Single cell cultures and delayed addition studies suggested that the stimulatory effect of IL-10 was directly mediated on the progenitor cells. The cells generated in response to FL + IL-7 + IL-10 appeared to be almost exclusively proB cells, as shown by their expression of B220, CD24, CD43, and lack of expression of c mu, myeloid, erythroid, and T-cell surface antigens. Although IL-10 also enhanced kit ligand (KL) + IL-7-induced proliferation of Lin-Sca-1(+)c-kit+ progenitor cells, the resulting cells were predominantly myeloid progeny. Accordingly, FL + IL-7 + IL-10 was 100-fold more efficient in stimulating production of proB cells than KL + IL-7 + IL-10. In contrast to its ability to stimulate the earliest phase of proB cell formation and proliferation, IL-10 inhibited growth of proB cells generated in response to FL + IL-7. Analysis of CD19 expression on cells generated in FL + IL-7 + IL-10 showed that almost all cells generated under these conditions lacked expression of CD19, in contrast to cells generated in the absence of IL-10, which were predominantly CD19(+). Replating of sorted CD19(+) and CD19(-) proB cells in FL + IL-7 or FL + IL-7 + IL-10 showed that IL-10 efficiently blocked growth of CD19(+), but not CD19(-) cells. Both CD19(-) and CD19(+) cells expressed lambda5 and VpreB , shown to be specific for B-cell progenitors. In addition, sorted CD19(-) cells generated CD19(+) cells in response to FL + IL-7. Thus, IL-10 has a dual regulatory effect on early B-cell development from primitive murine bone marrow progenitor cells in that it enhances FL + IL-7-induced proB-cell formation and growth before acquisition of CD19 expression, whereas growth of CD19(+) proB cells is inhibited.

Leptin stimulates fetal and adult erythroid and myeloid development.

The ob gene product, leptin, has been shown in several studies to be involved in weight control and recombinant leptin recently has entered clinical trials to treat obesity. The leptin receptor (OB-R/B219) is expressed in a variety of protein isoforms not only in the central nervous system, but also in reproductive, and hematopoietic tissues. We reported recently that the OB-R/B219 was associated with a variety of hematopoietic lineages as well as the small fraction of cells containing the long-term reconstituting hematopoietic stem cells. Herein we report that leptin significantly stimulates the proliferation and differentiation of yolk sac cells and fetal liver cells and stimulates directly hematopoietic precursors. Leptin alone can increase the number of macrophage and granulocyte colonies, and leptin plus erythropoietin act synergistically to increase erythroid development. These data show that leptin has a significant, direct effect on early hematopoietic development and can stimulate the differentiation of lineage-restricted precursors of the erythrocytic and myelopoietic lineages. These observations along with a recent report strongly support our previous hypothesis that leptin has an unanticipated important role in hematopoietic and immune system development.

Effect of antimicrobial agents on root surface caries, alveolar bone loss, and microflora in rice rats.

Two antimicrobial agents, 9-aminoacridine (0.2%) and minocycline (0.2%), were evaluated for their efficacy in inhibiting root surface caries, bone loss, and microflora in rice rats. A solution of 5000 ppm fluoride was used as a positive control for the inhibition of root surface caries, and double-distilled water was used as a negative control group. Each rat was treated by having its molar teeth swabbed 2 X per day with the prescribed agent in its group for nine weeks. Root caries reduction in the minocycline and fluoride groups was not significantly different, but the reduction was significantly greater than in the 9-aminoacridine group, with the caries score in all three groups being significantly less than that in the water control. Bone loss reduction for the minocycline group was significantly greater than that for any other group.

Inhibition of root surface caries in rice rats: use of a sodium fluoride dentifrice.

A sodium fluoride-containing dentifrice (Gleem) was evaluated for its efficacy to inhibit root surface caries in the rice rat. The dentifrice was diluted 50/50 with water so that the slurry contained 500 ppm fluoride. This slurry, a solution of 5000 ppm fluoride, and demineralized water were applied to the molar teeth twice daily for 10 weeks. Another group of rats was given 50 ppm fluoride in the drinking water. There was significantly less root surface caries in all groups of rats which received fluoride than in the demineralized water control animals. However, none of the fluoride preparations inhibited the loss of alveolar bone.

Effect of cheese, with and without sucrose, on dental caries and recovery of Streptococcus mutans in rats.

The objective of this study was to determine the effect of aged and young cheddar cheese with and without added sucrose on dental caries and the associated recovery of implanted Streptococcus mutans. Very little caries was observed in rats consuming cheese without sucrose. There was an increase in caries in rats fed cheeses with 20% sucrose, but this increase was not significant. There was significantly greater caries activity in rats fed standard diets containing 20% or 5% sucrose (SLS or MIT 305) than in rats fed cheeses containing 20% sucrose. Rats fed cheese or powdered diets containing sucrose had significantly higher frequency of recovery and higher levels of S. mutans infection than did rats fed cheese containing no sucrose. This study confirms the low cariogenic potential and possible cariostatic activity of cheddar cheese in rats. Since cheddar cheese with sucrose did not significantly interfere with S. mutans implantation, the cariostatic mechanism is apparently unrelated to a direct antimicrobial effect on S. mutans.

Anticariogenic effects of tea in rats.

Teas varying in fluoride and tannin concentration were evaluated in rats for anticariogenic activity. There was a direct correlation between fluoride in tea and the inhibition of sulcal caries in rats, whereas no relationship was observed between tannin and this type of lesion. Teas also had a significant effect on caries progression and imparted a black stain to the teeth.