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Inhomogeneity of the circulating BFU‐E regulation in sickle cell anaemia: accessory cells properties and BFU‐E growth factor response pattern
Author(s) -
Croizat Helena,
Nagel Ronald L.
Publication year - 1993
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1993.tb03105.x
Subject(s) - medicine , endocrinology , cell culture , chemistry , immunology , biology , genetics
Summary. Sickle cell anaemia (SS) patients with low (<9%) HbF levels (LFSS) are characterized by an increased number of circulating BFU‐E in active DNA synthesis, and release of burst promoting activity (BPA) by unstimulated low density (LD) adherent cells. In contrast, circulating BFU‐E from SS patients with high (>9%) HbF levels (HFSS) are normal in number, largely in resting phase, and their LD cells do not release BPA‐like activity. We report now that in LFSS patients, adherent cell depletion decreases BFU‐E growth in culture and apparent BFU‐E cycling. Furthermore, addition of conditioned media (CM) from LD cells of LFSS patients restored cycling BFU‐E expression in culture. Neutralization analysis with anti‐GM‐CSF antibody demonstrated that GM‐CSF is, at least, one factor responsible for BPA activity present in this CM. Thus, GM‐CSF is constitutively produced by unstimulated monocytes in LFSS patients. In contrast, HFSS patients' adherent cell depletion increases cycling of BFU‐E in culture. CM from HFSS patients inhibits BFU‐E expression in culture. Hence, LD adherent cells from HFSS patients may release a yet unknown inhibitor factor(s). In addition, we report a distinct response pattern in SS patients' BFU‐E to growth factor (GM‐CSF, IL‐3): (a) LFSS patients have a BFU‐E population, equally responsive to GM‐CSF and IL‐3; (b) HFSS patients, have a subset of BFU‐E exclusively dependent on IL‐3 (20–40% of the circulating BFU‐E). This pattern is very similar to that of normal BFU‐E. In conclusion, BFU‐E from LFSS patients represent an actively proliferating population, equally responsive to GM‐CSF and IL‐3, controlled by constitutively produced GM‐CSF, suggesting a unique BFU‐E behaviour in SS patients with low HbF levels and high haemopoietic stress. The heterogeneous regulation of BFU‐E in SS disease seems to be the epiphenomenon of HbF levels, and not vice versa.