Eva Cramer, PhD
Department of Cell Biology
The process of inflammation involves hemodynamic changes, increases in endothelial and epithelial permeability and the accumulation of leukocytes in various organs of the body. To reach the site of infection, the neutrophils and monocytes must traverse the endothelium of blood vessels and frequently the epithelium lining the infected organ. Leukocytes are capable of migrating across every epitheliuin in the body regardless of epithelial shape, thickness or permeability. However, how they are to do this is not understood. To examine this phenomenon, we have developed in vitro models of a microvessel wall and an organ epithelia. Using these systems we have studied the direct effects of various inflammatory mediators on the endothelium or epithelium itself or on the process of neutrophil and monocyte transendothelial or transepithelial migration. The effect of leukocyte, chemoattractant and/or permeability factors on the disassembly, reassembly and permeability of the epithelial occluding junctions are being examined. A permeability factor, which opens occluding junctions, has been found in human serum and is being isolated and characterized.
Recently, we have become interested in the interaction of leukocytes with virus infected epithelium. Using an in vitro model of an influenza-infected epithelium, we have begun to examine: a)how leukocytes are attached to the site of viral infections, b)recognize influenza-infected cells, c)when in the replication cycle this occurs and if there is a relationship between leukocyte viral binding molecules and, d)other leukocyte surface receptors. In addition, we are interested in the consequences of leukocyte accumulation on the permeability of the virus-infected epithelium and the effect of leukocyte traversion through the occluding junctions on the polarized budding of influenza virus as well as on the asymmetric distribution of endogenous and viral proteins in the epithelial cell membrane.
- Conyers, C., Milks, L., Conklyn, M., Showell, H., and Cramer, E. 1990. A factor in serum which lowers the resistance and opens the tight junctions of MDCK cells. Am. J. Physiol. 259 (Cell Physiol. 28), C577C585.
- Cramer, E., The ability of leukocytes to cross tight junctions. In: The Tight Junction. Ed. M. Cereijido, The Telford Press, Caldinece, New Jersey, In Press.
- Migliorisi, G., Folkes, E., Pawlowski, N., and Cramer, E., 1987. In vitro studies of human monocyte migration across endothelium in response to leukotriene B4 and MetLeuPhe. Am. J. Pathol. 127:157167.
- Ratcliffe, 0., Noun, S., and Cramer, E., 1988. Differences in the ability of neutrophils and monocytes to traverse epithelial occluding junctions. J. Leukocyte Biology.