Selective differentiation and proliferation of hematopoietic cells induced by recombinant human interleukins.

Abstract

Effects of recombinant human interleukins on hematopoiesis were explored by using suspension cultures of mononuclear cells of human umbilical-cord blood and bone marrow. The results showed that interleukin 5 induced the selective differentiation and proliferation of eosinophils. After 3 weeks in culture with interleukin 5, essentially all nonadherent cells in both bone marrow and cord blood cell cultures became eosinophilic myelocytes. Culture of the same cells with interleukin 4 resulted in the selective growth of OKT3' lymphocytes. However, OKT3' cells did not develop if the bone marrow cells were depleted of OKT3'/OKT11+ cells prior to the culture, indicating that interleukin 4 induced the proliferation of a subpopulation of resting T cells present in cord blood and bone marrow cell preparations. In suspension cultures of bone marrow cells and cord blood cells grown in the presence of interleukin 3, basophilic, eosinophilic, and neutrophilic myelocytes and macrophages developed within 2 weeks. By 3 weeks, however, the majority of nonadherent cells became eosinophilic myelocytes. In contrast to mouse bone marrow cell cultures, neither interleukin 3 nor a combination of interleukins 3 and 4 induced the differentiation of mast cells in human bone marrow or cord blood cell cultures.

The underestimated role of basophils in Ph+ chronic myeloid leukaemia

“…In the human system, the most potent basophil differentiation factor is interleukin‐3 (IL‐3) 29, 30, 31. This growth factor has been described to induce basophil differentiation and maturation in hematopoietic stem and progenitor cells, but also promotes the viability and activation of mature blood basophils 29, 30, 31, 32.…”

The role of the bone marrow in allergy and asthma

“…However, the precise stage at which the mast cell pathway diverges from the Eo-Bas0 one is unknown. Progenitors in cultures of human fetal liver cells, cord blood, or bone marrow differentiate into mast cells and basophils by using combinations of SCF and IL-3 (31,(33)(34)(35)(38)(39)(40)(41)(42). The immunophenotype of mast cells is distinct from that of basophils and eosinophils (43).…”

“…Lineagespecific cytokine effects on differentiated cells, which retain hemopoietic cytokine receptors on their surface, result in "activation" or "phenotype switching": IL-3, IL-5, and GM-CSF can activate and prevent apoptosis of basophils and eosinophils (42,59); G-CSF and GM-CSF do the same for neutrophils (60). Autocrine stimulation by eosinophils, basophils, or mast cells of their own differentiation and/or activation is thus possible, since they produce a wide range of hemopoietic and proinflammatory cytokines, including IL-3, IL-4, IL-5, IL-6, and GM-CSF (33,(61)(62)(63)(64)(65)(66)(67)(68)(69).…”

The identification and characterization of umbilical cord blood-derived human basophils

“…Human IgE receptor-positive cell lines with basophil-like characteristics such as KU812 have low receptor densities [7] and degranulate poorly (personal observation), whereas HMC-1 cells, used as a human mast cell model, have little or no message for the Fc⑀RI ␣ and ␤ subunits and hence have little surface Fc⑀RI expression [8,9]. As an alternative approach, basophils have been grown in vitro from precursor cells using various interleukins as differentiation factors [10][11][12][13][14][15][16][17]. In most of these studies, progenitors in bone marrow or cord blood exposed to interleukin-3 (IL-3), interleukin-5, or a combination of both, give rise to a majority of eosinophils with basophils and basophil/eosinophil hybrids making up the next most abundant cell population.…”