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Interleukin-4 (IL-4) has distinct hematopoietic activities, primarily as a costimulant with other cytokines to enhance colony formation of hematopoietic progenitors. We investigated the influence of IL-4 on stromal cell-supported long-term cultures (LTCs) of normal human bone marrow. Addition of IL-4 to LTCs of unseparated bone marrow or highly enriched CD34+ cells resulted in a significant increase of myeloid progenitors in the nonadherent, as well as in the stromal cell-adherent cell populations. In contrast, the total cell number was not influenced by IL-4, suggesting a selective effect on primitive progenitor cells. Cord blood cells or CD34+ bone marrow cells were incubated with stem cell factor (SCF) and/or IL-4 in stromal cell-free cultures. In these experiments, a twofold to fivefold increase of myeloid progenitor cells was observed in the presence of SCF and IL-4 as compared with SCF alone. Preincubation of the stromal cell cultures with IL-4 resulted in an enhanced adherence of CD34+ cells to the stromal layer. Secretion of hematopoietic growth factors produced by the stromal cells, such as granulocyte-macrophage colony-stimulating factor (G-CSF), and IL-1, was inhibited by IL-4. Thus, the increase of hematopoietic progenitors in LTCs, as observed in the presence of IL-4, can be at least partially explained by a costimulation of SCF and IL-4 on primitive progenitor cells and by an enhancement of hematopoietic cells to stroma. The downregulation of CSFs by IL-4 might prevent the expansion of the mature hematopoietic cell compartment. 相似文献
996.
化学修饰为小干扰RNA(siRNA)治疗面临的诸多挑战提供了解决方法。此综述考察现有的各种siRNA修饰方法,包括RNA和双链siRNA结构的各个方面。然后考察化学修饰siRNA的应用,重点关注其作用的专一性(消除免疫反应和杂交依赖性的脱靶作用)和转运方法,同时对酶稳定性和效价也进行了讨论。 相似文献
997.
J Vinet M Zwam IM Dijkstra N Brouwer HRJ Weering A Watts M Meijer MR Fokkens V Kannan D Verzijl HF Vischer MJ Smit R Leurs K Biber HWGM Boddeke 《British journal of pharmacology》2013,168(6):1375-1387
Background and Purpose
Induction of cellular migration is the primary effect of chemokine receptor activation. However, several chemokine receptor-like proteins bind chemokines without subsequent induction of intracellular signalling and chemotaxis. It has been suggested that they act as chemokine scavengers, which may control local chemokine levels and contribute to the function of chemokines during inflammation. This has been verified for the chemokine-like receptor proteins D6 and DARC as well as CCX-CKR. Here, we provide evidence for an additional biological function of human (h)CCX-CKR.Experimental Approach
We used transfection strategies in HEK293 and human T cells.Key Results
Co-expression of hCCX-CKR completely inhibits hCXCR3-induced chemotaxis. We found that hCCX-CKR forms complexes with hCXCR3, suggesting a relationship between CCX-CKR heteromerization and inhibition of chemotaxis. Moreover, negative binding cooperativity induced by ligands both for hCXCR3 and hCCX-CKR was observed in cells expressing both receptors. This negative cooperativity may also explain the hCCX-CKR-induced inhibition of chemotaxis.Conclusions and Implications
These findings suggest that hCCX-CKR prevents hCXCR3-induced chemotaxis by heteromerization thus representing a novel mechanism of regulation of immune cell migration. 相似文献998.
Van den Herik-Oudijk IE; Ter Bekke MW; Tempelman MJ; Capel PJ; Van de Winkel JG 《Blood》1995,86(9):3302-3307
Most Ig receptors exist as multi-subunit complexes with a unique ligand binding alpha chain and a common signaling FcR gamma-chain. The myeloid Fc gamma RIIa (CD32) appears unique among FcR because both ligand- binding and signaling capacity are found in the alpha chain. Within the cytoplasmic tails of Fc gamma RIIa and FcR gamma-chain similar, but not identical, activatory motifs (ITAMs) have been defined, in which tyrosines play an important role. Previously, Fc gamma RIIa-ITAM was shown to be critical for both proximal and distal activatory functions in IIA1.6 B-cell transfectants. Triggering of interleukin-2 (IL-2) release and antigen presentation was absent in Fc gamma RIIa, but not in FcR gamma-chain receptor complexes. We now assessed the capacity of Fc gamma RIIa wild-type and Fc gamma RIIa/gamma chimeric molecules to trigger IL-2 production and antigen presentation by B cells. Both of these functions could solely be triggered by receptors containing the FcRIIa was capable of functional interaction with FcR gamma-chain, thus reconstituting the capacity to trigger IL-2 release and antigen presentation. These data document qualitative differences between Fc receptor ITAMs. 相似文献
999.
Mircea Balasa Ellen Gelpi MJ Rey Jordi Vila Lluís Ramió‐Torrentà Ana Ma Quiles Granado Ricard Molina Latorre Hubert Lepidi Didier Raoult Albert Saiz 《Brain pathology (Zurich, Switzerland)》2014,24(3):230-238
Central nervous system Whipple's disease (CNS‐WD) with clinically isolated neurological involvement is a rare condition fatal without an early diagnosis. We aimed to present clinical and neuropathological features of three cases of pre‐ or post‐mortem polymerase chain reaction confirmed CNS‐WD with distinct clinical presentation, outcome and pathological findings. One patient had an acute onset with spinal and brainstem involvement and died without CNS‐WD diagnosis after 14 weeks. Neuropathology showed extensive inflammatory and necrotizing lesions with abundant foamy periodic‐acid‐Schiff (PAS)+ macrophages. The second patient had a subacute evolution with late CNS‐WD diagnosis and death occurring 18 months after onset despite antibiotic treatment. Brain examination showed inflammatory lesions in the brainstem, thalamus and cerebellum, and abundant foamy PAS+ macrophages. The third case was diagnosed within 4 weeks of onset and treated with an excellent response. He died after a disease‐free period of 24 months of unrelated causes. Neuropathology showed cystic residual lesions devoid of microorganisms without inflammatory reaction. CNS‐WD may have an acute or subacute course with variable response to treatment. Accordingly, subjacent lesions may be those of a severe acute necrotizing encephalitic process or subacute inflammatory lesions involving diencephalic, brainstem, cerebellar and spinal regions. Chronic, cavitary brain lesions may be sequelae of a successful treatment. Early diagnosis should allow appropriate treatment and improve prognosis. 相似文献
1000.
Pelinck MJ; De Vos M; Dekens M; Van der Elst J; De Sutter P; Dhont M 《Human reproduction (Oxford, England)》1998,13(4):960-963
The aim of the present study was to investigate pregnancy rates ensuing
from transfer of embryos with multinucleated blastomeres. In our in- vitro
fertilization (IVF)/intracytoplasmic sperm injection (ICSI) programme, 1735
embryo transfers were performed from January 1, 1995 to August 31, 1996. In
136 of these transfers at least one embryo with one or more multinucleated
blastomeres was present per transfer (study group). For each of these 136
transfers, two matched controls with transfer of exclusively mononucleated
embryos were selected (control group). Matching was carried out according
to age, method of fertilization (IVF or ICSI), number of transferred
embryos and quality score of transferred embryos. In the study group, there
were eight transfers of exclusively multinucleated embryos from which one
pregnancy ensued and 128 transfers in which multinucleated and
mononucleated embryos were transferred together leading to 23 pregnancies.
The overall clinical pregnancy rate per transfer was 16.9% in the study
group versus 28.7% in the control group (P = 0.01). The ongoing pregnancy
rate per transfer was 13.2% in the study group versus 23.2% in the control
group (P = 0.03). The implantation rate per transferred embryo was 6.0% in
the study group versus 11.3% in the control group (P = 0.003). This study
shows that embryos with one or more multinucleated blastomeres have a
poorer implantation potential than embryos with mononucleated blastomeres.
Transfer of embryos with multinucleated blastomeres should hence only be
considered when insufficient numbers of embryos with only mononucleated
blastomeres are present.
相似文献