Impact of sex and age on bone marrow immune responses in a murine model of trauma-hemorrhage

2007 ◽  
Vol 102 (1) ◽  
pp. 113-121 ◽  
Author(s):  
Christian P. Schneider ◽  
Martin G. Schwacha ◽  
Irshad H. Chaudry
Keyword(s):  
Bone Marrow ◽  
Immune Responses ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
Young Male ◽  
Midline Laparotomy ◽  
Specific Effects ◽  
Age Related ◽  
Macrophage Colony ◽  
Young Mice

Although studies have demonstrated that trauma markedly alters the bone marrow immune responses, sex and age are crucial determinants under such conditions and have not been extensively examined. To study this, 21- to 27-day-old (premature), 6- to 8-wk-old (mature), and 20- to 24-mo-old (aged) male and female (proestrus) C3H/HeN mice were sham operated or subjected to trauma (i.e., midline laparotomy) and hemorrhagic shock (30 ± 5 mmHg for 90 min) followed by fluid resuscitation. Twenty-four hours after resuscitation, bone marrow cells were harvested. Trauma-hemorrhage induced an increased number of the early pluripotent stem cell-associated bone marrow cell subsets (Sca1+CD34−CD117+/−lin+/−) in young mice. The CD117+proportion of these cell subsets increased in mature proestrus females, but not in males. Aged males displayed significant lower numbers of Sca1+CD34−CD117+/−lin+/−cells compared with young male mice. Trauma-hemorrhage also increased development of granulocyte/macrophage progenitor cells (CD11b+Gr-1+). Proliferative responses to granulocyte macrophage colony-stimulating factor were maintained in mature and aged proestrus females, but decreased in young mice and mature males. Augmented differentiation into monocyte/macrophage lineage in mature and aged proestrus females was observed and associated with the maintained release of TNF-α and IL-6. Conversely, increased IL-10 and PGE2production was observed in the male trauma-hemorrhage groups. Thus, sex- and age-specific effects in bone marrow differentiation and immune responses after trauma-hemorrhage occur, which are likely to contribute to the sex- and age-related differences in the systemic immune responses under such conditions.

Lidocaine depresses splenocyte immune functions following trauma-hemorrhage in mice

2006 ◽  
Vol 291 (5) ◽  
pp. C1049-C1055 ◽  
Author(s):  
Takashi Kawasaki ◽  
Mashkoor A. Choudhry ◽  
Martin G. Schwacha ◽  
Kirby I. Bland ◽  
Irshad H. Chaudry
Keyword(s):  
Bone Marrow ◽  
Cell Proliferation ◽  
Immune Responses ◽  
Cytokine Production ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
Sham Operation ◽  
Mapk Activation ◽  
Midline Laparotomy ◽  
Marrow Cells

Traumatic and/or surgical injury as well as hemorrhage induces profound suppression of cellular immunity. Although local anesthetics have been shown to impair immune responses, it remains unclear whether lidocaine affects lymphocyte functions following trauma-hemorrhage (T-H). We hypothesized that lidocaine will potentiate the suppression of lymphocyte functions after T-H. To test this, we randomly assigned male C3H/HeN (6–8 wk) mice to sham operation or T-H. T-H was induced by midline laparotomy and ∼90 min of hemorrhagic shock (blood pressure 35 mmHg), followed by fluid resuscitation (4× shed blood volume in the form of Ringer lactate). Two hours later, the mice were killed and splenocytes and bone marrow cells were isolated. The effects of lidocaine on concanavalin A-stimulated splenocyte proliferation and cytokine production in both sham-operated and T-H mice were assessed. The effects of lidocaine on LPS-stimulated bone marrow cell proliferation and cytokine production were also assessed. The results indicate that T-H suppresses cell proliferation, Th1 cytokine production, and MAPK activation in splenocytes. In contrast, cell proliferation, cytokine production, and MAPK activation in bone marrow cells were significantly higher 2 h after T-H compared with shams. Lidocaine depressed immune responses in splenocytes; however, it had no effect in bone marrow cells in either sham or T-H mice. The enhanced immunosuppressive effects of lidocaine could contribute to the host's enhanced susceptibility to infection following T-H.

scholarly journals CONTRIBUTION OF DIFFERENT CELL TYPES TO THE GENETIC CONTROL OF IMMUNE RESPONSES AS A FUNCTION OF THE CHEMICAL NATURE OF THE POLYMERIC SIDE CHAINS (POLY-L-PROLYL AND POLY-DL-ALANYL) OF SYNTHETIC IMMUNOGENS

1972 ◽  
Vol 135 (5) ◽  
pp. 1009-1027 ◽  
Author(s):  
G. M. Shearer ◽  
Edna Mozes ◽  
Michael Sela
Keyword(s):  
Bone Marrow ◽  
Immune Responses ◽  
Genetic Control ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
High Responder ◽  
Side Chains ◽  
Low Responder ◽  
Synthetic Polypeptide ◽  
Marrow Cells

Genetic regulation of immunological responsiveness was studied at the cellular level by comparing the limiting dilutions of immunocompetent cells from spleen, thymus, and bone marrow of high and low responders as a function of the poly-L-prolyl and poly-DL-alanyl side chains of two synthetic polypeptide immunogens. The spleens of immunized and unimmunized high responder DBA/1 mice were found to contain respectively, 18- and 7-fold more limiting precursor cells specific for (Phe, G)-A--L than the spleens of SJL low responder donors. These results, using a synthetic polypeptide built on multichain poly-DL-alanine, confirm the findings reported for polypeptides built on multichain poly-L-proline (1, 2), that there is a direct correlation between immune response potential and the relative number of immunocompetent precursors stimulated. Cell cooperation between thymocytes and bone marrow cells was demonstrated for both (T, G)-Pro--L and (Phe, G)-A--L. Limiting dilutions of thymus and bone marrow cells in the presence of an excess amount of the complementary cell type indicated an eightfold lower number of detected (T, G)-Pro--L-specific precursors in DBA/1 (low responder) marrow when compared with SJL (high responder) marrow. No differences were observed in the frequency of relevant high and low responder thymocytes for the (T, G)-Pro--L immunogen. These results are similar to those reported for the (Phe, G)-Pro--L (3). In contrast to the cellular studies reported for the Pro--L series of immunogens, the marrow and thymus cell dilution experiments for (Phe, G)-A--L revealed genetically associated differences in both the marrow and thymus populations of immunocytes from high (DBA/1) and low (SJL) responders. In addition to a fivefold difference in limiting marrow cell precursors (similar to that seen in the Pro--L studies), a striking difference was observed between the helper cell activity of high responder DBA/1 and low responder SJL thymocytes. This difference was indicated by the observation that low responder thymocyte dilutions followed the predictions of the Poisson model, whereas dilutions of high responder thymocytes did not conform to Poisson statistics. Transfers of allogeneic thymus and marrow cell mixtures from DBA/1 and SJL donors confirmed the syngeneic dilution studies showing that the genetic defect of immune responsiveness to (Phe, G)-A--L is expressed at both the thymus and marrow immunocompetent cell level. The parameters presently known for genetic control of immune responses specific for (Phe, G) (Ir-1 gene) and for Pro--L (Ir-3 gene) have been compared. The Ir-1 and Ir-3 genes are not only distinct by genetic linkage tests (to H-2) (5, 6, 9), but they are also seen to be different by cellular studies. Furthermore, expression of low responsiveness within a given cell population was shown to depend on the chemical structure of the whole immunogenic macromolecule.

scholarly journals CONTRIBUTION OF BONE MARROW CELLS AND LACK OF EXPRESSION OF THYMOCYTES IN GENETIC CONTROLS OF IMMUNE RESPONSES FOR TWO IMMUNOPOTENT REGIONS WITHIN POLY-(PHE,GLU)-POLY-PRO--POLY-LYS IN INBRED MOUSE STRAINS

1971 ◽  
Vol 134 (1) ◽  
pp. 141-161 ◽  
Author(s):  
Edna Mozes ◽  
G. M. Shearer
Keyword(s):  
Bone Marrow ◽  
Immune Responses ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
Genetic Defect ◽  
Precursor Cells ◽  
Immunocompetent Cells ◽  
Mouse Strains ◽  
Limiting Dilution ◽  
Marrow Cells

Previous cellular studies on the genetic regulation of immunological responsiveness for two immunopotent regions within the branched chain synthetic polypeptide (Phe, G)-Pro--L demonstrated a direct correlation between the number of detectable immunocompetent splenic precursor cells and the response patterns of SJL, DBA/1, and F1 mice (21). In order to establish the cellular origin(s) of the genetic defect, the present study first demonstrated that thymus and bone marrow cell cooperation was required for (Phe, G)- and Pro--L-specific immune responses. Secondly, limiting dilution experiments, in which several graded and limiting inocula of marrow cells were mixed with a non-limiting number of 108 thymocytes and injected into irradiated, syngeneic recipients, indicated that the low responsiveness of the SJL and DBA/1 strains to the (Phe, G) and Pro--L specificities, respectively, could be attributed to a reduced number of precursor cells found in bone marrow. About five times more marrow precursors were detected in SJL mice for Pro--L than for (Phe, G), whereas about five times as many precursor cells were estimated for (Phe, G) as for Pro--L in the DBA/1 strain. These differences are similar to those obtained using spleen cells from unimmunized SJL and DBA/1 donors (21), and indicate that these genetically determined variations in responsiveness can be accounted for by differences in the frequencies of monospecific populations of immunocompetent cells present in bone marrow. In contrast, limiting dilution transfers of thymocytes or thymus-derived cells with an excess of syngeneic marrow cells resulted in equally frequent (Phe, G) and Pro--L responses for both SJL ad DBA/1 strains. This finding in conjunction with the observation that the generation of (Phe, G)- and Pro--L-specific responses were associated in individual recipients injected with limiting inocula of thymocytes indicated that a single population of thymocytes was stimulated by (Phe,G)-Pro--L. Therefore, it is improbable that the thymic population of immunocompetent cells contributes to expression of these genetically controlled defects.

scholarly journals Treatment with at Homeopathic Complex Medication Modulates Mononuclear Bone Marrow Cell Differentiation

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Beatriz Cesar ◽  
Ana Paula R. Abud ◽  
Carolina C. de Oliveira ◽  
Francolino Cardoso ◽  
Raffaello Popa Di Bernardi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Differentiation ◽  
Mononuclear Cells ◽  
Bone Marrow Cells ◽  
Ex Vivo ◽  
Marrow Cell ◽  
Macrophage Colony ◽  
Total Bone Marrow

A homeopathic complex medication (HCM), with immunomodulatory properties, is recommended for patients with depressed immune systems. Previous studies demonstrated that the medication induces an increase in leukocyte number. The bone marrow microenvironment is composed of growth factors, stromal cells, an extracellular matrix and progenitor cells that differentiate into mature blood cells. Mice were our biological model used in this research. We now reportin vivoimmunophenotyping of total bone marrow cells andex vivoeffects of the medication on mononuclear cell differentiation at different times. Cells were examined by light microscopy and cytokine levels were measuredin vitro. Afterin vivotreatment with HCM, a pool of cells from the new marrow microenvironment was analyzed by flow cytometry to detect any trend in cell alteration. The results showed decreases, mainly, in CD11b and TER-119 markers compared with controls. Mononuclear cells were used to analyze the effects ofex vivoHCM treatment and the number of cells showing ring nuclei, niche cells and activated macrophages increased in culture, even in the absence of macrophage colony-stimulating factor. Cytokines favoring stromal cell survival and differentiation in culture were inducedin vitro. Thus, we observe that HCM is immunomodulatory, either alone or in association with other products.

scholarly journals CD34+ human marrow cells that express low levels of Kit protein are enriched for long-term marrow-engrafting cells

Blood ◽  
1996 ◽  
Vol 87 (10) ◽  
pp. 4136-4142 ◽  
Author(s):  
I Kawashima ◽  
ED Zanjani ◽  
G Almaida-Porada ◽  
AW Flake ◽  
H Zeng ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
In Utero ◽  
Fetal Sheep ◽  
Hematopoietic Stem ◽  
Show Evidence ◽  
Marrow Cells

Using in utero transplantation into fetal sheep, we examined the capability of human bone marrow CD34+ cells fractionated based on Kit protein expression to provide long-term in vivo engraftment. Twelve hundred to 5,000 CD34+ Kit-, CD34+ Kit(low), and CD34+ Kit(high) cells were injected into a total of 14 preimmune fetal sheep recipients using the amniotic bubble technique. Six fetuses were killed in utero 1.5 months after bone marrow cell transplantation. Two fetuses receiving CD34+ Kit(low) cells showed signs of engraftment according to analysis of CD45+ cells in their bone marrow cells and karyotype studies of the colonies grown in methylcellulose culture. In contrast, two fetuses receiving CD34+ Kit(high) cells and two fetuses receiving CD34+ Kit- cells failed to show evidence of significant engraftment. Two fetuses were absorbed. A total of six fetuses receiving different cell populations were allowed to proceed to term, and the newborn sheep were serially examined for the presence of chimerism. Again, only the two sheep receiving CD34+ Kit(low) cells exhibited signs of engraftment upon serial examination. Earlier in studies of murine hematopoiesis, we have shown stage-specific changes in Kit expression by the progenitors. The studies of human cells reported here are in agreement with observations in mice, and indicate that human hematopoietic stem cells are enriched in the Kit(low) population.

Age related changes in hemopoietic capacity of bone marrow cells

1989 ◽  
Vol 48 (1) ◽  
pp. 91-99 ◽  
Author(s):  
A. Sharp ◽  
D. Zipori ◽  
J. Toledo ◽  
S. Tal ◽  
P. Resnitzky ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Age Related ◽  
Age Related Changes ◽  
Marrow Cells

scholarly journals Interleukin-6 enhances murine megakaryocytopoiesis in serum-free culture

Blood ◽  
1990 ◽  
Vol 75 (12) ◽  
pp. 2286-2291 ◽  
Author(s):  
K Koike ◽  
T Nakahata ◽  
T Kubo ◽  
T Kikuchi ◽  
M Takagi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Interleukin 6 ◽  
Bone Marrow Cells ◽  
Early Stage ◽  
Colony Growth ◽  
Colony Stimulating Factor ◽  
Serum Free ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Marrow Cells

We investigated the effect of interleukin-6 (IL-6) on murine megakaryocytopoiesis in a serum-free culture system. The addition of IL- 6 to a culture containing interleukin-3 (IL-3) resulted in a significant increase in the number of megakaryocyte colonies by bone marrow cells of normal mice. The megakaryocytic progenitors that survive exposure to 5-fluorouracil (5-FU) exhibited a more significant response to IL-6 and IL-3. Polyclonal anti-IL-6 antibody neutralized the stimulatory effect of IL-6 on megakaryocyte colony growth supported by IL-3. Delayed addition experiments and replating experiments of blast cell colonies showed that megakaryocytic progenitors are supported by IL-3 in the early stage of the development but require IL- 6 for their subsequent proliferation and differentiation. In addition, IL-6 increased the size of megakaryocytes in granulocyte-macrophage- megakaryocyte colonies. The combination of granulocyte colony- stimulating factor or granulocyte-macrophage colony stimulating factor with IL-3 resulted in an increase in the granulocyte-macrophage colony growth of bone marrow cells of 5-FU-treated mice or normal mice, respectively, but had little effect on the enhancement of pure and mixed megakaryocyte colony growth. These results suggest that IL-6 plays an important role in murine megakaryocytopoiesis.

scholarly journals Hematopoietic Recovery after Transplantation CD117+B220- (lacZ+) Bone Marrow Cells in Lethally Irradiated Mice

2008 ◽  
Vol 51 (1) ◽  
pp. 37-41 ◽  
Author(s):  
Miroslav Hodek ◽  
Jiřina Vávrová ◽  
Zuzana Šinkorová ◽  
Jaroslav Mokrý ◽  
Stanislav Filip
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Repair Process ◽  
Whole Body ◽  
Lacz Gene ◽  
Colony Forming Units ◽  
The Difference ◽  
Macrophage Colony ◽  
Marrow Cells

Experiments presented here were aimed at the description of hematopoiesis repair and in vivo homing of transplanted separated CD117+B220–bone marrow cells after whole-body lethal irradiation at LD 9Gy. ROSA 26 mice were used as donors of marrow cells for transplantation [B6;129S/Gt (ROSA)26Sor] and were tagged with lacZ gene, and F2 hybrid mice [B6129SF2/J] were used as recipients of bone marrow transplanted cells. Hematopoiesis repair was provided by transplantation, both suspension of whole bone marrow cells (5x106) and isolated CD117+B220–cells (5x104). Mice survived up to thirty days after irradiation. We demonstrated that transplantation of suspension of whole bone marrow cells led to faster recovery of CFU-GM (Granulocyte-macrophage colony forming units) in bone marrow and in the spleen too. It is not clear what the share of residential and transplanted cells is in the repair process. Our results demonstrate that sufficient hematopoietic repair occurs after transplantation of CD117+B220–(lacZ+) in lethally irradiated mice, and the difference in CFU-GM numbers in the bone marrow and spleen found on day 8 posttransplant has no influence on the survival of lethally irradiated mice (30 days follow-up).

scholarly journals A Model for Sequestration of the Transmission Stages of Plasmodium falciparum: Adhesion of Gametocyte-Infected Erythrocytes to Human Bone Marrow Cells

2000 ◽  
Vol 68 (6) ◽  
pp. 3455-3462 ◽  
Author(s):  
Nicola J. Rogers ◽  
Belinda S. Hall ◽  
Jacktone Obiero ◽  
Geoffrey A. T. Targett ◽  
Colin J. Sutherland
Keyword(s):  
Bone Marrow ◽  
Plasmodium Falciparum ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Mature Stage ◽  
High Avidity ◽  
Necrosis Factor Alpha ◽  
Marrow Cells

ABSTRACT With the aim of developing an appropriate in vitro model of the sequestration of developing Plasmodium falciparumsexual-stage parasites, we have investigated the cytoadherence of gametocytes to human bone marrow cells of stromal and endothelial origin. Developing stage III and IV gametocytes, but not mature stage V gametocytes, adhere to bone marrow cells in significantly higher densities than do asexual-stage parasites, although these adhesion densities are severalfold lower than those encountered in classical CD36-dependent assays of P. falciparum cytoadherence. This implies that developing gametocytes undergo a transition from high-avidity, CD36-mediated adhesion during stages I and II to a lower-avidity adhesion during stages III and IV. We show that this adhesion is CD36 independent, fixation sensitive, stimulated by tumor necrosis factor alpha, and dependent on divalent cations and serum components. These data suggest that gametocytes and asexual parasites utilize distinct sets of receptors for adhesion during development in their respective sequestered niches. To identify receptors for gametocyte-specific adhesion of infected erythrocytes to bone marrow cells, we tested a large panel of antibodies for the ability to inhibit cytoadherence. Our results implicate ICAM-1, CD49c, CD166, and CD164 as candidate bone marrow cell receptors for gametocyte adhesion.

scholarly journals Effects of neuraminidase on the regulation of erythropoiesis

Blood ◽  
1984 ◽  
Vol 63 (4) ◽  
pp. 784-788 ◽  
Author(s):  
VF LaRussa ◽  
F Sieber ◽  
LL Sensenbrenner ◽  
SJ Sharkis
Keyword(s):  
Bone Marrow ◽  
Colony Formation ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
Colony Growth ◽  
Mouse Bone Marrow ◽  
Continuous Exposure ◽  
Low Concentrations ◽  
High Concentrations ◽  
Marrow Cells

Abstract In this article, we present evidence that sialic acid-containing surface components play a role in the regulation of erythropoiesis. A 1- hr exposure of mouse bone marrow cells to high concentrations of neuraminidase reduced erythroid colony formation. Coculture of 10(6) untreated thymocytes with neuraminidase-treated bone marrow cells restored erythroid colony growth. Neuraminidase-treated thymocytes retained their ability to suppress erythroid colony formation by untreated marrow cells, but lost their ability to enhance erythroid colony formation. Continuous exposure to low concentrations of neuraminidase enhanced erythroid bone marrow cell colony growth in response to a suboptimal dose of erythropoietin.

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