Hypoxia in the thymus: role of  oxygen tension in thymocyte survival

Hale, Laura P.; Braun, Rosemary; Gwinn, William M.; Greer, Paula K.; Dewhirst, Mark W.

doi:10.1152/ajpheart.00682.2001

Cited by 71 publications

(66 citation statements)

References 33 publications

(47 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…5) and widespread staining with the PIM hypoxia marker (SI Fig. 8B) consistent with the previous study of Hale et al (25). The intensity of staining with the anti-PIM antibody was met only by bone marrow cells isolated from the SP ''tip'' region (Fig.…”

Section: Discussionsupporting

confidence: 89%

“…8B). These results confirm the overall hypoxic state of thymic tissue as shown previously (25). In the bone marrow fractions, non-SP cells demonstrated only a small shift of PIM staining as compared with the saline control mice (R1 region in Fig.…”

Section: Distribution Of Different Hematopoietic Subsets Along a Ho Dyesupporting

confidence: 91%

“…3). The thymus is also more accessible to oxygen microelectrode measurements and pO2 values of Ϸ10 mmHg have been estimated (25). Thus, only the very small fraction of HSCs and closely associated cells appear to exist at around this low level of oxygen whereas most of the bone marrow tissue containing the committed and differentiating progenitors appears to be relatively well oxygenated.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxia

Parmar

Mauch

Vergilio³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

779

629

View full text Add to dashboard Cite

The interaction of stem cells with their bone marrow microenvironment is a critical process in maintaining normal hematopoiesis. We applied an approach to resolve the spatial organization that underlies these interactions by evaluating the distribution of hematopoietic cell subsets along an in vivo Hoechst 33342 (Ho) dye perfusion gradient. Cells isolated from different bone marrow regions according to Ho fluorescence intensity contained the highest concentration of hematopoietic stem cell (HSC) activity in the lowest end of the Ho gradient (i.e., in the regions reflecting diminished perfusion). Consistent with the ability of Ho perfusion to simulate the level of oxygenation, bone marrow fractions separately enriched for HSCs were found to be the most positive for the binding of the hypoxic marker pimonidazole. Moreover, the in vivo administration of the hypoxic cytotoxic agent tirapazamine exhibited selective toxicity to the primitive stem cell subset. These data collectively indicate that HSCs and the supporting cells of the stem cell niche are predominantly located at the lowest end of an oxygen gradient in the bone marrow with the implication that regionally defined hypoxia plays a fundamental role in regulating stem cell function.Hoechst perfusion ͉ stem cell niche ͉ oxygen gradient ͉ pimonidazole ͉ tirapazamine

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Distribution Of Different Hematopoietic Subsets Along a Ho Dyesupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxia

Parmar

Mauch

Vergilio³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

779

629

View full text Add to dashboard Cite

show abstract

“…The stem cells are prone to use anaerobic metabolism, perhaps as a means to reduce genotoxic stress associated with reactive oxygen species generated from aerobic metabolism 18 . Oxygen electrode and hypoxia marker drug studies have demonstrated that the thymus of mice is heterogeneously hypoxic 6,15 , but in this tissue there is no evidence for HIF1-regulated gene expression 15 . Recently it was shown that lymphocyte motility in lymph nodes is affected by pO 2 , with motility decreasing with oxygen content 26 .…”

Section: Regulation Of Hif1 By Hypoxiamentioning

confidence: 98%

“…Examples of relatively hypoxic normal tissues include pericentral vein cells in the liver 12 , portions of the retina (in the dark) 13 , spinous layer of the epidermis 14 , the thymus 6,15 , renal tubular epithelium 16 , myocardium (particularly during exercise) 17 and subregions of the bone marrow that are enriched for stem cells 18 . Hypoxia has diverse roles in the function of these normal tissues.…”

Section: Regulation Of Hif1 By Hypoxiamentioning

confidence: 99%

Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response

2008

Self Cite

View full text Add to dashboard Cite

Hypoxia and free radicals, such as reactive oxygen and nitrogen species, can alter the function and/or activity of the transcription factor hypoxia-inducible factor 1 (HIF1). Interplay between free radicals, hypoxia and HIF1 activity is complex and can influence the earliest stages of tumour development. The hypoxic environment of tumours is heterogeneous, both spatially and temporally, and can change in response to cytotoxic therapy. Free radicals created by hypoxia, hypoxia-reoxygenation cycling and immune cell infiltration after cytotoxic therapy strongly influence HIF1 activity. HIF1 can then promote endothelial and tumour cell survival. As discussed here, a constant theme emerges: inhibition of HIF1 activity will have therapeutic benefit.Virchow first described the abnormal structure of tumour vessels using contrast agents in human tumours as early as the mid 1800s 1 . A few decades later, Goldman was among the first to suggest that angiogenesis was associated with tumour growth 2 . A number of other investigators in the nineteenth and early twentieth centuries evaluated tumour angiogenesis, using techniques such as microangiography, vascular casting and window chamber models. Warren has reviewed this early work in great detail 3 . Folkman illuminated the crucial role of tumour angiogenesis by hypothesizing that tumour growth was dependent upon angiogenesis and that, if angiogenesis could be inhibited, it could maintain tumour deposits in a quiescent state 4 . These early works set the stage for the concept that tumours require angiogenesis to provide a nutrient supply. Although it is well-established that angiogenesis occurs in nearly all human solid tumours, it does not occur in an efficient manner, leading to spatial and temporal inadequacies in delivery of oxygen and other nutrients. These inefficiencies in nutrient delivery lead to a brutal cycle of unsatisfied demand by the tumour, which drives continued aberrant angiogenesis.The transcription factor hypoxia-inducible factor 1 (HIF1) plays an important part in tumour progression by upregulating genes that control angiogenesis, meta-stasis and resistance to oxidative stress. It also controls the switch to anaerobic metabolism, which can maintain cell NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript viability under hypoxic conditions. Further, HIF1 activity can promote treatment resistance by promoting endothelial and tumour cell survival after cytotoxic therapy. The mechanisms that control HIF1 activity are complex and are influenced by microenvironmental factors involving hypoxia, oxidative and nitrosative stress.In this Review we will discuss four important and interrelated aspects of tumour hypoxia. First, we will define the hypoxic response, discussing its relevance in influencing tumour cell survival, behaviour and angiogenesis. We will examine the physiological factors that contribute to hypoxia, emphasizing a perspective based on spatial and temporal dysfunction of tumour microcirculation. The question of whethe...

show abstract

Normal and Benign Reactive Hematopoietic Tissues

Valli¹

2007

Veterinary Comparative Hematopathology

View full text Add to dashboard Cite

Hypoxia in the thymus: role of oxygen tension in thymocyte survival

Cited by 71 publications

References 33 publications

Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxia

Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxia

Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response

Normal and Benign Reactive Hematopoietic Tissues

Contact Info

Product

Resources

About