| Innovative strategies for the oral delivery of drugs and peptides Trends in Biotechnology, Volume 16, Issue 4, 1 April 1998, Pages 152-157 Alessio Fasano Abstract Conventional forms of administration for nonabsorbable drugs and peptides often rely on parenteral injection, because the intestinal epithelium represents a major barrier to the oral absorption of these therapeutic agents. Recently, a number of innovative drug-delivery approaches have been developed, including entrapment within small vesicles and passage through the space between adjacent intestinal cells. This article reviews some of the most promising techniques currently available for oral delivery and their possible practical applications for the delivery of vaccines and drugs for the treatment of clinical conditions that require frequent, chronic parenteral administration. Abstract | Full Text | PDF (344 kb) |
| Leaky guts and lipid rafts Trends in Microbiology, Volume 13, Issue 12, 1 December 2005, Pages 560-563 Erin C. Boyle and B. Brett Finlay Abstract The intestinal epithelium functions as a physical barrier separating luminal microorganisms from the underlying immune system. There is compelling evidence that several intestinal diseases are associated with the translocation of commensal bacteria across the epithelial barrier. Recent work has identified a novel mechanism by which normally non-invasive enteric bacteria breach the intestinal epithelium during periods of inflammation. Abstract | Full Text | PDF (136 kb) |
| Transcellular Diapedesis Is Initiated by Invasive Podosomes Immunity, Volume 26, Issue 6, 22 June 2007, Pages 784-797 Christopher V. Carman, Peter T. Sage, Tracey E. Sciuto, Miguel A. de la Fuente, Raif S. Geha, Hans D. Ochs, Harold F. Dvorak, Ann M. Dvorak and Timothy A. Springer Summary Diapedesis is critical for immune system function and inflammatory responses. This occurs by migration of blood leukocytes either directly through individual microvascular endothelial cells (the “transcellular” route) or between them (the “paracellular” route). Mechanisms for transcellular pore formation in endothelium remain unknown. Here we demonstrate that lymphocytes used podosomes and extended “invasive podosomes” to the surface of, and ultimately form transcellular pores through, the endothelium. In lymphocytes, these structures were dependent on Src kinase and the actin regulatory protein WASP; inhibition of podosome formation selectively blocked the transcellular route of diapedesis. In endothelium, membrane fusion events dependent on the SNARE-containing membrane fusion complex and intracellular calcium were required for efficient transcellular pore formation in response to podosomes. These findings provide insights into basic mechanisms for leukocyte trafficking and the functions of podosomes. Summary | Full Text | PDF (3703 kb) |
Copyright © 1982 The Biophysical Society. All rights reserved.
Biophysical Journal, Volume 38, Issue 2, 143-152, 1 May 1982
doi:10.1016/S0006-3495(82)84541-4
Research Article
A. Essig
Theoretical analysis of transepithelial active Na transport is often based on equivalent electrical circuits comprising discrete parallel active and passive pathways. Recent findings show, however, that Na+ pumps are distributed over the entire basal lateral surface of epithelial cells. This suggests that Na+ that has been actively transported into paracellular channels may to some extent return to the apical (mucosal) bathing solution, depending on the relative conductances of the pathways via the tight junctions and the lateral intercellular spaces. Such circulation, as well as the relative conductance of cellular and paracellular pathways, may have an important influence on the relationships between parameters of transcellular and transepithelial active transport and metabolism. These relationships were examined by equivalent circuit analysis of active Na transport, Na conductance, the electromotive force of Na transport, the "stoichiometry" of transport, and the degree of coupling of transport to metabolism. Although the model is too crude to permit precise quantification, important qualitative differences are predicted between "loose" and "tight" epithelia in the absence and presence of circulation. In contrast, there is no effect on the free energy of metabolic reaction estimated from a linear thermodynamic formalism. Also of interest are implications concerning the experimental evaluation of passive paracellular conductance following abolition of active transport, and the use of the cellular voltage-divider ratio to estimate the relative conductances of apical and basal lateral plasma membranes.