ISSN:0737-1454    

DOI:10.1002/stem.5530070102

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractIt is clear from extensive in vitro data that different subsets of lymphocytes stimulate and inhibit the growth of hematopoietic stem and progenitor cells. In order to clarify the complexity of the network between regulatory lymphocytes and hematopoietic target cells, we have examined the stimulatory and inhibitory effects derived from different lymphoid subsets. The regulatory influence of lymphocytes is transmitted mainly through the release of cytokines including the interleukins, granulocyte‐macrophage colony‐stimulating factor, tumor necrosis factor‐beta and the interferons, all of which have nonspecific effects on a variety of hematopoietic cells. Since these cytokines amplify the effects of other, more lineage‐specific cytokines (e.g., erythropoietin, thrombopoietin and granulocyte or macrophage colony‐stimulating factor) on the proliferation and differentiation of progenitor cells, the present review supports the conclusion that lymphoid subsets play a critical role in ensuring an optimal hematopoietic response to specifi

ISSN:0737-1454    

DOI:10.1002/stem.5530070103

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractA high proportion of acute myeloid leukemias (AML) recently investigated for their capacity to synthesize biologically active bioregulatory molecules was found to accumulate messenger (m) RNA and to produce membrane‐bound or ‐secreted forms of stimulating factors for granulocyte, macrophage and mixed granulocyte‐macrophage colony growth. Blast cells have also been found to secrete interleukin 1, tumor necrosis factor‐alpha, interleukin 6, and to express receptors for various growth factors as well. However, growth factors like interleukin 2 and interleukin 3 have not been identified as AML products, and several other factors including interleukin 4, interleukin 5, etc. need further evaluation. Responsiveness of clonogenic leukemic cells to exogenous growth‐promoting factors in vitro suggests a possible role of these biomolecules in the course of these disorders. Important evidence for the crucial role of growth factors, at least in some subtypes of AML, has been provided by demonstrating constitutive growth factor production by leukemic cells and their autonomous in vitro growth which is dependent on autocrine secretion of a specific growth factor. The concert of mechanisms providing stimulatory and inhibitory signals for hematopoiesis, which is adapted to the various physiological requirements of the organism, may have multiple defects in AML. This leads to successive steps of malfunctioning of cells, which finally express a fully malignant phenotype. In addition, these derangements also lead to defects in accessory cells on the level of mediator communication. However, there is evidence for autonomous growth promotion of AML blast by constitutive production of growth factors active in an autocrine fashion (GM‐CSF, G‐CSF, interleukin 6) and by recruitment of accessory cells to increase CSF supply (GM‐CSF, G‐CSF) via molecules such as interleukin 1 and TNF‐alpha in a paracrine fashion. Molecular analysis of transformed hematopoietic cells has revealed changes of the genome, e.g., insertion of viral genetic information or cytogenetic fractures at DNA sites controlling growth factor gene activation. These events appear to be crucial in the induction of uncontrolled growth factor expression promoting oncogenic transformation of hematopoiet

ISSN:0737-1454    

DOI:10.1002/stem.5530070104

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractTo determine the extent accessory cells mediate the effects of recombinant human granulocyte‐macrophage colony‐stimulating factor (rhGM‐CSF) on human hemopoietic progenitors in vitro, we added this hemopoietin to liquid cultures of single CD34‐positive marrow cells. These were selected on a fluorescence‐activated cell sorter using the HPCA‐1 (My10) antibody. Myeloid, erythroid and a few mixed clones developed in 13% of wells in the apparent absence of accessory cells at the beginning of culture. Although accessory cells were generated quickly from the myeloid progenitors and could have mediated the action of rhGM‐CSF, this was not the case in the majority of the erythroid clones in which no other cell types were recorded. We conclude that rhGM‐CSF can act directly on a subset of erythroid progenitors and probably induces a substantial number of myeloid

ISSN:0737-1454    

DOI:10.1002/stem.5530070105

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractThe effects of recombinant human hemopoietic growth factors on early and late human erythroid progenitors (BFU‐e and CFU‐e) were investigated in serum‐free cultures. Recombinant human erythropoietin (rhEpo) induced the formation of not only human CFU‐e‐derived colonies but also human BFU‐e‐derived bursts. Recombinant human interleukin 3 (rhIL‐3) alone did not induce the formation of human BFU‐e‐derived bursts and human CFU‐e‐derived colonies. In the presence of rhEpo, rhIL‐3 dose dependently increased the number of bursts stimulated by rhEpo, although rhIL‐3 did not have the augmentative effect on human CFU‐e growth. On the other hand, rhIL‐3 did not stimulate the formation of murine BFU‐e‐derived bursts, and murine IL‐3 did not stimulate the formation of human BFU‐e‐derived bursts. The results indicated that the burst‐promoting activity of IL‐3 was species‐specific between human and murine cells. Recombinant human GM‐CSF (rhGM‐CSF) or recombinant human G‐CSF (rhG‐CSF) failed to induce human burst formation and did not augment the effect of rhEpo on human burst formation. The results of the present study suggest that in vitro, IL‐3 can stimulate BFU‐e in collaboration with Epo, but GM‐CSF and G‐CSF

ISSN:0737-1454    

DOI:10.1002/stem.5530070106

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractWe investigated the capacity of recombinant human granulocyte‐macrophage colony‐stimulating factor (rhGM‐CSF) to enhance the function of neutrophils. Neutrophil function was measured in terms of N‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP)‐induced luminol‐dependent chemiluminescence (LDCL). LDCL of fMLP‐stimulated neutrophils was enhanced up to 4.5 fold following preincubation with rhGM‐CSF. This enhancement depended on the length of preincubation, reaching an optimal level at 120 min. The dose‐response relationship for fMLP‐induced LDCL of neutrophils preincubated with rhGM‐CSF revealed that half‐maximum enhancement was achieved at an approximately 20‐fold higher concentration than that of colony‐forming units in culture‐derived colony formation. These results suggest that differences in dose dependency may be explained by differences in the distribution of receptor(s) for GM‐CSF. This may also enable GM‐CSF to affect the hematopoietic system, which contains cells at various levels of differentiation, th

ISSN:0737-1454    

DOI:10.1002/stem.5530070107

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractThe effect of epidermal growth factor (EGF) on the in vitro growth of human malignant tumors was compared in serum‐supplemented (n = 54) and serum‐free (N = 41) media at clonal density to determine the true EGF dependency of tumors. In the complete absence of serum at a 1,000 cells/cm2seeding inoculation (approximately 100–200 adherent cells), EGF increased growth by>50% in 27 of 41 specimens (66%), and growth increased by 100% or more in 18 of these EGF‐sensitive tumors. In 12 serum‐free cultures (29%), in vitro growth failed to occur without EGF. With 10% serum supplementation and a lower cell density (250 cells/cm2), EGF increased growth by>50% in 34 of 54 specimens (63%), of which 25 had more than a 100% increase. The maximum growth induced by EGF in serum was usually seen in those tumors already capable of moderate in vitro growth. No difference in response to EGF was detected between specimens from primary tumors (n = 24) and those from metastases (n = 30).Under the stringent culture conditions of complete absence of serum and with tumors seeded at a low cell number, EGF stimulated most primary or metastatic human tumors to establish and sustain short‐term in vitro growth s

ISSN:0737-1454    

DOI:10.1002/stem.5530070108

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

ISSN:0737-1454    

DOI:10.1002/stem.5530070109

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

ISSN:0737-1454    

DOI:10.1002/stem.5530070110

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY