Vol. 282, Issue 4, H1467-H1477, April 2002
Hypoxia in the thymus: role of oxygen tension in thymocyte
survival
Laura P.
Hale1,3,
Rod D.
Braun2,
William M.
Gwinn1,3,
Paula
K.
Greer1, and
Mark W.
Dewhirst1,2
1 Departments of Pathology and
2 Radiation Oncology and the 3 Cell and
Molecular Biology Program, Duke University, Durham, North Carolina
27710
Our previous studies using oxygen
microelectrodes showed that the thymus is grossly hypoxic under normal
physiological conditions. We now have investigated how oxygen tension
affects the thymus at the cellular and molecular level. Adducts of the
hypoxia marker drug pimonidazole accumulated in foci within the cortex
and medulla and at the corticomedullary junction, consistent with the
presence of widespread cellular hypoxia in the normal thymus.
Hypoxia-associated pimonidazole accumulation was decreased but not
abrogated by oxygen administration. Genes previously reported to be
induced by hypoxia were expressed at baseline levels in the normal
thymus, indicating that physiological adaptation to hypoxia occurred.
Despite changes in thymus size and cellularity, thymic
PO2 did not change with age. Combined assays
for hypoxia and cell death showed that hypoxia achieved using either
hypoxic gas mixtures or high-density culture in normoxia decreased
spontaneous thymocyte apoptosis in vitro. Taken together, these
data suggest that regulatory mechanisms exist to maintain thymic
cellular hypoxia in vivo and that oxygen tension may regulate thymocyte
survival both in vitro and in vivo.
apoptosis; gene regulation