Developmental abnormalities of terminal deoxynucleotidyl transferase positive bone marrow cells and thymocytes in New Zealand mice: effects of prostaglandin E1.
The enzyme TdT was used as a marker with which to study the ontogeny of primitive lymphopoietic cells in NZ strain mice. A marked accumulation of abnormally large, rapidly proliferating TdT+ cells was seen in the subcapsular region of the thymus cortex in the NZB and NZB/W mice. This abnormal accumulation of TdT+ thymocytes was most pronounced in the NZB/W hybrid and persisted for at least the first 16 wk of life. In addition, significantly elevated percentages of TdT+ bone marrow cells (presumptive prothymocytes) were present in NZB, NZW, and NZB/W mice between 1 and 4 wk of age, with the highest mean peak levels occurring in the NZB strain. Treatment of both normal and adrenalectomized BALB/c and NZB/W mice with pharmacologic doses (7 to 10 mg/kg) of PGE1 caused a marked, dose-dependent decrease in thymus weight and thymus cell number within 12 to 18 hr. Histologic and cell separation studies showed that this was due to the selective depletion of PNA+ TdT+ cortical thymocytes. Similarly, PGE1 caused a reversible, dose-dependent decrease in the percentage of TdT+ bone marrow cells. In contrast, PGF2 alpha, which is not therapeutically active against autoimmunity in NZB/W mice, had no detectable effect on TdT+ bone marrow cells or thymocytes in BALB/c or NZB/W mice. These results directly document the existence of abnormalities in the development of lymphopoietic precursor cells in the bone marrow and thymus cortex of NZ strain mice prior to the onset of autoimmune phenomena. The results also raise the possibility that the therapeutic efficacy of exogenous PGE1 in autoimmune NZ strain mice may be related, at least in part, to its ability to rectify the abnormal development of these early lymphoid cells.
D000315:Adrenalectomy; D000527:Alprostadil; D000818:Animals; D001853:Bone Marrow / Q000201:enzymology / Q000254:growth & development / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004253:DNA Nucleotidylexotransferase / Q000378:metabolism*; D004254:DNA Nucleotidyltransferases / Q000378:metabolism*; D037102:Lectins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB / Q000276:immunology*; D019887:Peanut Agglutinin; D010641:Phenotype; D011458:Prostaglandins E / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D013950:Thymus Gland / Q000201:enzymology / Q000254:growth & development / Q000473:pathology*
D037102:Lectins; D019887:Peanut Agglutinin; D011458:Prostaglandins E; D004254:DNA Nucleotidyltransferases; D004253:DNA Nucleotidylexotransferase; D000527:Alprostadil