The interaction of 125I-colony-stimulating factor-1 with bone marrow-derived macrophages.
The interaction of 125I-colony-stimulating factor-1 with bone marrow-derived macrophages.
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发表时间：
1986-03
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通讯作者：
L. Guilbert;E. Stanley
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作者：
L. Guilbert;E. Stanley
集落刺激因子-1刺激静止培养的小鼠骨髓巨噬细胞(BMM)进入DNA合成的滞后期为10~12h，观察了滞后期BMM对125I-CSF-1的结合、解离、内化和降解。静止的BMM表达约5×10(4)个细胞表面受体位点/细胞，但含有额外的隐蔽位点(约10(5)个/细胞)，可在37℃的10分钟内出现在细胞表面。对2℃(Kd小于或等于2×10(-13)M)和37℃(Kd约为4×10(-10)M)的结合反应的研究与单一类别细胞表面位点的存在一致。细胞表面125I-CSF-1在2-37℃温度漂移后的消失是两个竞争的一级过程、内化和解离的结果。内化(t1/2=1.6min)的频率是解离(t1/2=9.6min)的6倍。在内化后，10-15%的细胞内CSF-1被快速降解，而其余的85-90%被氯喹敏感的一级过程缓慢降解(t1/2大于3.5h)。在37℃下摄取~(125)I-CSF-1的研究证实并扩展了这些发现。在加入~(125)I-CSF-1后，细胞表面受体迅速下调(T1/2约7分钟)，直到20-60%先前存在的表面受体位点消失后，它们的替换才开始。尽管受体的替换最初来自隐池，后来通过从头合成和/或受体循环(4个分子/细胞/S处于稳定状态)，但细胞表面的受体数量仍然很少。这一过程导致BMM在细胞内积累大量的125I-CSF-1(大于10(5)个分子/细胞)。因此，尽管CSF-1与BMM和腹膜渗出液巨噬细胞的结合、解离和内化的动力学相似，但表现出更高增殖反应的BMM降解生长因子的速度要慢12倍。
The colony-stimulating factor, CSF-1, stimulates cultured quiescent murine bone marrow-derived macrophages (BMM) to enter DNA synthesis with a lag phase of 10-12 h. The binding, dissociation, internalization, and degradation of 125I-CSF-1 by BMM during the lag phase were investigated. Quiescent BMM express approximately 5 X 10(4) cell surface receptor sites/cell but contain additional cryptic sites (approximately 10(5)/cell) that can appear at the cell surface within 10 min at 37 degrees C. Studies of the binding reaction at both 2 degrees C (Kd less than or equal to 2 X 10(-13) M) and 37 degrees C (Kd approximately 4 X 10(-10) M) are consistent with the existence of a single class of cell surface sites. The disappearance of cell surface 125I-CSF-1 following a 2-37 degrees C temperature shift results from two, competitive, first order processes, internalization and dissociation. Internalization (t1/2 = 1.6 min) is 6 times more frequent than dissociation (t1/2 = 9.6 min). Following internalization, 10-15% of the intracellular CSF-1 is rapidly degraded whereas the remaining 85-90% is slowly degraded by a chloroquin-sensitive first order process (t1/2 greater than 3.5 h). These findings were confirmed and extended by studies of the uptake of 125I-CSF-1 at 37 degrees C. Following addition of 125I-CSF-1, cell surface receptors are rapidly down-regulated (t1/2 approximately 7 min) and their replacement does not commence until 20-60% of pre-existing surface receptor sites have disappeared. Despite receptor replacement, initially from the cryptic pool and later by de novo synthesis and/or receptor recycling (4 molecules/cell/s at steady state), the number of receptors at the cell surface remains low. The process results in the intracellular accumulation of large amounts of 125I-CSF-1 (greater than 10(5) molecules/cell) by BMM. Thus, whereas the kinetics of association, dissociation, and internalization of CSF-1 with BMM and peritoneal exudate macrophages are similar, BMM, which exhibit a higher proliferative response, degrade growth factor 12 times more slowly.