Abnormal myelocytic cell development in interleukin-2 (IL-2)-deficient mice: evidence for the involvement of IL-2 in myelopoiesis.
Mice lacking interleukin-2 (IL-2) developed a severe hematopoietic disorder characterized by the abnormal development of myeloid cells and neutropenia. Analysis of the bone marrow of IL-2-deficient (IL-2(-/-)) mice showed that the number of mature polymorphonuclear cells was decreased by 65% to 75%, and granulocyte/macrophage precursor cells were reduced by 50%. Bone marrow cells from IL-2(-/-) mice were unable to sustain myelopoiesis in lethally irradiated mice and in long-term bone marrow cultures (LTBMC). The addition of exogenous IL-2 to LTBMC of IL-2(-/-) cells partially restored hematopoietic progenitor activity. In the bone marrow of wild-type mice, immature (Mac-1(lo)) myeloid cells, including myeloblasts and promyelocytes, constitutively expressed the beta-chain of the IL-2R, and the number of Mac-1(lo)IL-2Rbeta+ cells was increased by twofold to threefold in IL-2(-/-) mice. During culture in the presence of IL-2 and the absence of stromal cells, Mac-1(lo)IL-2Rbeta+ immature myeloid cells proliferated and gave rise to mature granulocytes and macrophages. Collectively, these observations indicate that defective myelopoiesis in IL-2(-/-) mice is at least in part a consequence of their direct dependency on IL-2, and by regulating the growth of immature myeloid cells, IL-2 plays an important role in the homeostatic regulation of myelocytic cell generation.
Reya
T
T
Department of Microbiology, Division of Hematology and Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6076, USA.
Contractor
N V
NV
Couzens
M S
MS
Wasik
M A
MA
Emerson
S G
SG
Carding
S R
SR
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D006098:Granulocytes / Q000166:cytology / Q000502:physiology; D007376:Interleukin-2 / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology; D019891:Leukopoiesis / Q000187:drug effects; D051379:Mice; D008817:Mice, Mutant Strains; D009504:Neutrophils / Q000166:cytology / Q000502:physiology
D007376:Interleukin-2