Age-related differences in the effect of in vivo administration of indomethacin on hemopoietic cell lineages of the spleen and bone marrow of mice

During 21 days of indomethacin treatment, erythroid cells in the spleens of both young adult and older mice, and in the bone marrow of young adult mice, were increased significantly early, in treatment, relative to age-matched control organs, and remained high throughout treatment. During drug exposure, the numbers of myeloid cells in young adult bone marrow, but not spleen, were reduced, but in older mice these cells were elevated in both organs. Lymphoid cells in the young adult and older mouse spleens decreased and increased, respectively, during treatment, but were unchanged and decreased, respectively, in the bone marrow of young adult and older mice. Monocytemacrophage cells in the spleen were elevated but unchanged in the bone marrow of both age groups. During 14 days of indomethacin treatment of houng adult mice, the proportions of precursor cells in DNA synthesis of only the splenic erythroid lineage were increased. Thus, the major hemopoietic lineages in both the bone marrow and spleen are affected by exposure to indomethacin in a time-dependent and age-dependent manner. For all lineages studied, those of the bone marrow were least disturbed, and/or were first to recover, even during continued drug exposure.     

Age-related differences in the effect of in vivo administration of indomethacin on hemopoietic cell lineages of the spleen and bone marrow of mice.

During 21 days of indomethacin treatment, erythroid cells in the spleens of both young adult and older mice, and in the bone marrow of young adult mice, were increased significantly early in treatment, relative to age-matched control organs, and remained high throughout treatment. During drug exposure, the numbers of myeloid cells in young adult bone marrow, but not spleen, were reduced, but in older mice these cells were elevated in both organs. Lymphoid cells in the young adult and older mouse spleens decreased and increased, respectively, during treatment, but were unchanged and decreased, respectively, in the bone marrow of young adult and older mice. Monocyte-macrophage cells in the spleen were elevated but unchanged in the bone marrow of both age groups. During 14 days of indomethacin treatment of young adult mice, the proportions of precursor cells in DNA synthesis of only the splenic erythroid lineage were increased. Thus, the major hemopoietic lineages in both the bone marrow and spleen are affected by exposure to indomethacin in a time-dependent and age-dependent manner. For all lineages studied, those of the bone marrow were least disturbed and/or were first to recover, even during continued drug exposure.     

Functional potential of ectopic marrow autotransplants

Summary Ectopic autotransplants of the marrow tissue, form within 4 weeks, stable nodules which respond to erythropoietic modulation in a manner similar to other parts of the marrow. The findings indicate that these autotransplants are an integral part of the total hemopoietic mass.This work was supported by NIH grants AM25510 and AM70551 DOE contract DE-AS03-79EV00899.     

Differences in susceptibility of tissues to revascularization studied in ectopic implants

Summary The survival rate of implanted marrow is reduced when the tissue is transferred from one site to another within the first 24 hours but not more than 48 hours after the initial implantation. Splenic implants can be transferred at any time after implantation without affecting the survival rate. The observation suggests a difference in the sensitivity of the two tissues to the avascular period that they experience prior to initiation of angiogenesis.The work was supported by a grant from NIH. The author is recipient of a Career Research Development Award from NIAMDD.     

Peptidylarginine deiminase in rat and mouse hemopoietic cells

Summary Peptidylarginine (protein-L-arginine) deiminase activities have been demonstrated in extracts of rat and mouse peritoneal macrophages, bone marrow cells, splenic adherent cells, neutrophils, and mouse monocyte/macrophage cell lines. The enzyme in these cells is indistinguishable from the skeletal muscle enzyme with respect to immunochemical properties.     

Peptidylarginine deiminase in rat and mouse hemopoietic cells

Peptidylarginine (protein-L-arginine) deiminase activities have been demonstrated in extracts of rat and mouse peritoneal macrophages, bone marrow cells, splenic adherent cells, neutrophils, and mouse monocyte/macrophage cell lines. The enzyme in these cells is indistinguishable from the skeletal muscle enzyme with respect to immunochemical properties.     

The influence of a new antitumor agent on hemopoietic colony forming cells

Summary The cytostatic and immunsuppressive agent N-methyl-N--chloroethylbenzaldehyde hydrazone (B1) in invitro experiments has a stimulating effect on colony-forming culture (CFUc) of bone marrow from C57BL mice. This unusual behaviour, which is in contrast to other cytostatics, could also be observed in vitro with CFUc obtained from mice treated with therapeutic doses of B1 for 2 weeks. This stimulation is not a particular effect of B1 alone but seems to depend on a synergistic effect of the combination of B1 and the colony-stimulating activity (CSA) present in the serum from endotoxin-treated mice (MP) in the testing system. The results suggest that the described effect of B1 is due to an interference at the cell membrane of CFUc or their precursor cells.     

The influence of a new antitumor agent on hemopoietic colony forming cells

The cytostatic and immunsuppressive agent N'-methyl-N'-beta-chloroethylbenzaldehyde hydrazone (B1) in in-vitro experiments has a stimulating effect on colony-forming culture (CFUc) of bone marrow from C57BL mice. This unusual behaviour, which is in contrast to other cytostatics, could also be observed in vitro with CFUc obtained from mice treated with therapeutic doses of B1 for 2 weeks. This stimulation is not a particular effect of B1 alone but seems to depend on a synergistic effect of the combination of B1 and the colony-stimulating activity (CSA) present in the serum from endotoxin-treated mice (MP) in the testing system. The results suggest that the described effect of B1 is due to an interference at the cell membrane of CFUc or their precursor cells.     

The uptake of iodinated protein by spleen cells of guinea-pigs in vitro

Zusammenfassung 6×10^–10 g bis 10^–4 g J 125 Rinderserum-Albumin (BSA) bzw. 1,0×10^–7 bis 1,0×10^–6 g J 125 Rinderserum--Globulin (BGG) werden 3 × 10⁷ Milzzellen normaler Meerschweinchen in vitro angeboten. Unabhängig von der Höhe des Angebotes beträgt die Menge des aufgenommenen BSA 1%, die des aufgenommenen BGG 10% des Angebotes. Durch 4C Inkubations-temperatur wird die Aufnahme z.T. behindert. Die Aufnahme findet nach wenigen Sekunden Inkubationszeit statt und ist nach etwa 2–3 min abgeschlossen.

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The work was supported by a grant of the Stiftung Volkswagenwerk and of the Deutsche Forschungsgemeinschaft.     

Multinucleated giant cells in organ cultures of spleen

Riassunto In colture organotipiche di milza di embrione di pollo compaiono nella zona di contatto fra le superfici del terreno di coltura e dell'espianto cellule giganti polinucleate. Vengono analizzate le loro caratteristiche ultrastrutturali in base alle quali si evidenziano elementi di almeno 2 tipi. Ipotesi sono avanzate sulle loro possibili attività metaboliche.     

The in vitro effect of aprotinin upon spleen cells from normal and tumour-bearing mice exposed to PPD and tumour cells

Aprotinin (Trasylol) is shown to enhance the response of spleen cells from normal and tumour bearing mice to PPD nd tumour cells. This enhancement is greater in the tumour-bearing mice.     

The in vitro effect of aprotinin upon spleen cells from normal and tumour-bearing mice exposed to PPD and tumour cells

Summary A protinin (Trasylol) is shown to enhance the response of spleen cells from normal and tumour bearing mice to PPD and tumour cells. This enhancement is greater in the tumour-bearing mice.Acknowledgments. We are grateful to Bayer (U.K.) Limited for generous supplies of aprotinin. The PPD was supplied by the Ministry of Agriculture. The work was supported by a grant from the North of England Cancer Research Campaign.     

Interaction of thymic cells and hemopoietic stem cells. Enhancing effect on irradiated thymus repopulation]

In irradiated mice engrafted with hemopoietic cells, the thymus is repopulated more rapidly by bone marrow-derived than by spleen-derived cells. Admixing thymic cells with the restorative suspension stimulates the thymic repopulation by spleen-derived cells whereas it has no effect on the repopulation by bone marrow-derived cells.     

Donor origin of the in vitro hematopoietic microenvironment after marrow transplantation in mice

Summary Bone marrow stroma from radiochimeric mice was established in culture. The polymorphic enzyme glucose phosphate isomerase (GPI) was used to determine the proportions of donor and recipient present in the original bone marrow and in cultured stroma. Bone marrow initially containing 95% donor GPI, when cultured and subsequently passaged for up to 8 weeks remained about 70% donor GPI. We conclude that many cultured stromal cells are donor derived in our radiochimeras and these are probably of hematopoietic origin.     

Donor origin of the in vitro hematopoietic microenvironment after marrow transplantation in mice

Bone marrow stroma from radiochimeric mice was established in culture. The polymorphic enzyme glucose phosphate isomerase (GPI) was used to determine the proportions of donor and recipient present in the original bone marrow and in cultured stroma. Bone marrow initially containing 95% donor GPI, when cultured and subsequently passaged for up to 8 weeks remained about 70% donor GPI. We conclude that many cultured stromal cells are donor derived in our radiochimeras and these are probably of hematopoietic origin.     

Compartmentalized growth of hemopoietic stem cells within mouse Friend leukemic spleens

Summary A dose of 4000 rads (r) to the central portion of mouse spleens followed by Friend erythroleukemic virus infection created independent compartments where hemopoietic stem cells exhibited distinct growth kinetics. Rather than suggesting autonomous proliferation, the stem cell kinetics were indicative of the control excercised by the local microenvironment upon stem cell growth within each compartment.Acknowledgments. This work was supported in part by a grant (014077) from the American Medical Association Eduation and research Foundation, Chicago, Illinois. We also wish to thank Priscilla Brown and Peter Brown for their expertise and patience in preparing the photograph for this report.     

Separation of rabbit marrow myeloid cells

Riassunto Viene descritto un metodo per la separazione delle cellule mieloidi dal midollo osseo di coniglio. Questo metodo ha il vantaggio di essere molto rapido e consente di ottenere preparazioni di cellule mieloidi non ammassate, vitali e prive di elementi eritroidi e di piastrine.

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This study was aided by a grant from the Lady Tata Memorial Trust.     

Induction of hemopoietic chimerism in the caprine fetus by intraperitoneal injection of fetal liver cells

Summary Intraperitoneal injection of allogeneic liver cells from 43-day-old male fetuses into normal 60-day female goat fetuses resulted in persistent hemopoietic chimerism in surviving recipients without clinical evidence of graft-versus-host disease. Transplantation of normal fetal liver cells into preimmunocompetent goat fetuses affected with -D-mannosidosis may provide an alternative strategy for evaluating hemopoietic stem cell transplantation in the treatment of human lysosomal storage diseases.     

The influence of bacterial endotoxin on the formation of antibody-forming spleen cells in mice immunized with sheep red blood cells

Zusammenfassung Es wird berichtet, dass die simultane i.v. Injektion vonSerratia marcescens-Endotoxin mit i.p. verabfolgten Schafbluterythrocyten bei weissen Mäusen zu einer beschleunigten Bildung hämolysinbildender Milzzellen und zu einem verzögertem Abfall dieser kompetenten Zellen zwischen dem 7. und 30. Tage nach der Immunisierung führt. Eine echte Vermehrung plaquebildender Milzzellen wurde jedoch nicht gefunden. Weiterhin liess sich zeigen, dass die alleinige i.v. Injektion von bakteriellem Lipopolysaccharid eine mässige Proliferation von in geringer Zahl vorhandenen antikörperbildenden Milzzellen bewirkt.

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This work was supported by research grant No. Fi 115/1 of the Deutsche Forschungsgemeinschaft.