Tissue distribution of recombinant human tumor necrosis factor alpha derivative in mice
Chai, B.X.; Tang, Z.M.; Liu, X.W.; Tu, M.
Zhongguo Yao Li Xue Bao 20(4): 371-374
1999
ISSN/ISBN: 0253-9756 PMID: 10452128 Document Number: 511874
AIM: To study the tissue distribution and its mechanism of a new recombinant tumor necrosis factor alpha derivative (rhTNFalphaDa) in mice. METHODS: 125I-rhTNFalphaDa was prepared by Iodogen method. Tissue distribution of 125I-rhTNFalphaDa in mice was studied by determining radioactivity of tetrachloroacetic acid (TCA)- precipitable fraction in tissues. The isolated heart-lung perfusion study using 125I-rhTNFalphaDa perfusate was carried out to study the distribution characteristics of 125I-rhTNFalphaDa in lung. RESULTS: Except for thyroid, AUC of the TCA-precipitable 125I-rhTNFalphaDa in tissues was highest in lung, which was 12.2-fold of that in serum, while concentrations in other tissues were all lower than that in serum. Perfusion study in vitro revealed that the concentration of radio-labeled peptide in lung was higher than that in perfusate. On the contrary, level in heart was much lower than that in perfusate. The overall distribution of 125I-rhTNFalphaDa in lungs showed rapidlyequilibratory, dose-dependent, saturable, competitive, and highly affinitive, with Kd47.6 pmol cntdot L-1 and Bmax 348 fmol cntdot g-1 (lung tissue). CONCLUSION: The specific distribution of rhTNFalphaDa in lungs was its distinctive characteristics.