Transcellular Delivery of an Insulin-Transferrin Conjugate in Enterocyte-like Caco-2 Cells

1996 ◽  
Vol 85 (12) ◽  
pp. 1306-1311 ◽  
Author(s):  
Deven Shah ◽  
Wei-chiang Shen
2015 ◽  
Vol 209 (1) ◽  
pp. 2091OIA65
Author(s):  
Emilie Bourdonnay ◽  
Zbigniew Zasłona ◽  
Loka Raghu Kumar Penke ◽  
Jennifer M. Speth ◽  
Daniel J. Schneider ◽  
...  

1986 ◽  
Vol 250 (3) ◽  
pp. F503-F510
Author(s):  
R. D. Wright ◽  
J. R. Blair-West ◽  
J. F. Nelson

Secretion by the parotid gland of Na-replete and -depleted sheep was investigated by examining the effects of modifiers of ionic transfer on salivary composition and flow rate. These agents were infused into the arterial blood supply of the vascularly isolated gland in anesthetized sheep. Ouabain inhibited Na+-K+ exchange in the ducts caused by Na depletion and restored the [Na+], [K+], and osmolality to close to those of Na-replete saliva. Ouabain also inhibited Cl- -HCO3- exchange in the ducts in Na repletion and depletion. Amiloride partially inhibited Na+-K+ exchange in Na depletion without affecting Cl- -HCO3- exchange. Monensin potentiated Na+-K+ exchange in Na repletion and depletion. Amiloride and monensin gained access to the saliva, but furosemide and ethacrynic acid were almost totally excluded, and, up to 10(-3) M in blood, they did not affect salivary composition or flow rate. Methazolamide gained free access to saliva but was without effect. 4-Acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid at 10(-3) M slightly increased salivary [Na+] and [HPO4(2-)]. The results indicate potent effects of ouabain on basolateral Na+-K+ pumps and of amiloride and monensin on transcellular delivery of Na+ to these pumps, but ouabain had no effect on salivary flow rate until O2 consumption approached zero and secretion failed. The findings do not support a proposal that the salivary secretion depends on a Cl- -dependent furosemide-sensitive system energized by Na+-K+-ATPase-dependent Na pumps.


2010 ◽  
Vol 39 (1) ◽  
pp. 394-401 ◽  
Author(s):  
Melissa J. Simon ◽  
Woo Hyeun Kang ◽  
Shan Gao ◽  
Scott Banta ◽  
Barclay Morrison III

2015 ◽  
Vol 212 (5) ◽  
pp. 729-742 ◽  
Author(s):  
Emilie Bourdonnay ◽  
Zbigniew Zasłona ◽  
Loka Raghu Kumar Penke ◽  
Jennifer M. Speth ◽  
Daniel J. Schneider ◽  
...  

JAK-STAT signaling mediates the actions of numerous cytokines and growth factors, and its endogenous brake is the family of SOCS proteins. Consistent with their intracellular roles, SOCS proteins have never been identified in the extracellular space. Here we report that alveolar macrophages can secrete SOCS1 and -3 in exosomes and microparticles, respectively, for uptake by alveolar epithelial cells and subsequent inhibition of STAT activation. Secretion is tunable and occurs both in vitro and in vivo. SOCS secretion into lung lining fluid was diminished by cigarette smoking in humans and mice. Secretion and transcellular delivery of vesicular SOCS proteins thus represent a new model for the control of inflammatory signaling, which is subject to dysregulation during states of inflammation.


2020 ◽  
Vol 12 (565) ◽  
pp. eabb0580
Author(s):  
Malin Bern ◽  
Jeannette Nilsen ◽  
Mattia Ferrarese ◽  
Kine M. K. Sand ◽  
Torleif T. Gjølberg ◽  
...  

Needle-free uptake across mucosal barriers is a preferred route for delivery of biologics, but the efficiency of unassisted transmucosal transport is poor. To make administration and therapy efficient and convenient, strategies for the delivery of biologics must enhance both transcellular delivery and plasma half-life. We found that human albumin was transcytosed efficiently across polarized human epithelial cells by a mechanism that depends on the neonatal Fc receptor (FcRn). FcRn also transported immunoglobulin G, but twofold less than albumin. We therefore designed a human albumin variant, E505Q/T527M/K573P (QMP), with improved FcRn binding, resulting in enhanced transcellular transport upon intranasal delivery and extended plasma half-life of albumin in transgenic mice expressing human FcRn. When QMP was fused to recombinant activated coagulation factor VII, the half-life of the fusion molecule increased 3.6-fold compared with the wild-type human albumin fusion, without compromising the therapeutic properties of activated factor VII. Our findings highlight QMP as a suitable carrier of protein-based biologics that may enhance plasma half-life and delivery across mucosal barriers.


2018 ◽  
Vol 54 (80) ◽  
pp. 11304-11307 ◽  
Author(s):  
Peng Sun ◽  
Zhen Li ◽  
Jingyun Wang ◽  
Hui Gao ◽  
Xi Yang ◽  
...  

A dendritic catiomer with a metal–organic framework motif afforded improved protection to the mRNA payloads in biological milieu.


Neuron ◽  
2021 ◽  
Author(s):  
Kelly A. Chamberlain ◽  
Ning Huang ◽  
Yuxiang Xie ◽  
Francesca LiCausi ◽  
Sunan Li ◽  
...  

2012 ◽  
Vol 13 (3) ◽  
pp. 836-845 ◽  
Author(s):  
Lina Han ◽  
Yuefang Zhao ◽  
Lifang Yin ◽  
Ruiming Li ◽  
Yang Liang ◽  
...  

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