Interleukin-3 is a differentiation factor for human basophils.
The effect of recombinant human (rh) cytokines, interleukin-1 alpha (IL-1 alpha), interleukin-2 (IL-2), interleukin-3 (IL-3), interleukin-4 (IL-4), granulocyte/macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), monocyte/macrophage colony stimulating factor (M-CSF), interferon-alpha (IF-alpha), interferon-gamma (IF-gamma), and the tumor necrosis factor-alpha (TNF-alpha) on differentiation and function of metachromatic cells (MCS) was studied. Among all cytokines tested, rh interleukin-3 (rhIL-3) selectively induced a significant formation of MCS (IL-3: 1.1 +/- 0.6 x 10(5) v control: 0.02 +/- 0.15 x 10(5) MCS/mL suspension) and dose dependent increase in formation of intracellular histamine (IL-3, 100 U/mL: 95 +/- 23 ng/mL v control: 1.8 +/- 0.8 ng/mL) in a bone marrow suspension culture system (analyzed on day 14 of culture). Besides MCS, formation of eosinophils was observed in this culture system in the continuous presence of rhIL-3, whereas IL-3 pulse-stimulation for three hours and subsequent exposure to control medium induced growth of MCS but not of eosinophils. By combined immunofluorescence/toluidine blue staining, MCS were found to express a cell surface marker profile that corresponds to the immunological phenotype of peripheral blood basophils (MY-7(CD13)+, VIM12(CD11b)+, VIM2+, MAX1-, MAX24- and YB5B8-). Furthermore, cultured MCS expressed surface membrane receptors for IgE and could be triggered for nontoxic histamine release by a monoclonal anti-IgE antibody. To evaluate a possible influence of IL-3 on basophil function, studies were extended to freshly obtained blood basophils (healthy volunteers, n = 3). However, like all other cytokines tested, rhIL-3 failed to induce basophil histamine release. Taken together, our studies demonstrate that IL-3 is a differentiation factor for human basophils.
Valent
P
P
I. Medical Department, University of Vienna, Austria.
Schmidt
G
G
Besemer
J
J
Mayer
P
P
Zenke
G
G
Liehl
E
E
Hinterberger
W
W
Lechner
K
K
Maurer
D
D
Bettelheim
P
P
D000911:Antibodies, Monoclonal; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D001491:Basophils / Q000145:classification / Q000378:metabolism / Q000502:physiology*; D001853:Bone Marrow; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D007377:Interleukin-3 / Q000494:pharmacology*; D010641:Phenotype; D011961:Receptors, Fc / Q000032:analysis; D017455:Receptors, IgE; D011994:Recombinant Proteins / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000944:Antigens, Differentiation, B-Lymphocyte; D006133:Growth Substances; D007377:Interleukin-3; D011961:Receptors, Fc; D017455:Receptors, IgE; D011994:Recombinant Proteins; D007073:Immunoglobulin E