Levine J S, Pugh B J, Hartwell D, Fitzpatrick J M, Marshak-Rothstein A, Beller D I
Renal Section, Boston University Medical Center, MA.
Eur J Immunol. 1993 Nov;23(11):2951-8. doi: 10.1002/eji.1830231134.
Macrophages (M phi) from pre-diseased autoimmune-prone MRL mice (both MRL/+ and MRL/lpr) dramatically underproduce the cytokine interleukin-1 (IL-1) in comparison to M phi from a number of normal strains. In this study we show that IL-1 dysregulation by MRL M phi is fully expressed at birth, and that this defect does not change with time or the development of disease. We also constructed adult irradiation chimeras (consisting of A/J-->MRL and MRL-->A/J mice), and show that M phi isolated from these chimeras display a pattern of IL-1 production indistinguishable from that of the donor strain controls. Moreover, when we constructed a mixed chimera (A/J + MRL-->A/J, the A/J and MRL M phi coexisting within the same animal retained their individual patterns of IL-1 production when isolated by negative selection. Taken together, these results provide the first substantive evidence for an intrinsic defect (IL-1 dysregulation) in M phi from MRL autoimmune-prone mice.
与多种正常品系的巨噬细胞相比，来自患病前自身免疫易感MRL小鼠（MRL/+和MRL/lpr）的巨噬细胞（M phi）显著低水平产生细胞因子白细胞介素-1（IL-1）。在本研究中，我们表明MRL M phi对IL-1的调节异常在出生时就已完全表现出来，并且这种缺陷不会随时间或疾病的发展而改变。我们还构建了成年辐射嵌合体（由A/J→MRL和MRL→A/J小鼠组成），并表明从这些嵌合体中分离出的M phi显示出与供体品系对照无法区分的IL-1产生模式。此外，当我们构建一个混合嵌合体（A/J + MRL→A/J）时，通过阴性选择分离时，同一动物体内共存的A/J和MRL M phi保留了它们各自的IL-1产生模式。综上所述，这些结果为来自MRL自身免疫易感小鼠的M phi存在内在缺陷（IL-1调节异常）提供了首个实质性证据。
