Multiple tissues express alpha1-antitrypsin in transgenic mice and man

J. A. Carlson, B. B. Rogers, R. N. Sifers, H. K. Hawkins, M. J. Finegold, S. L C Woo

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

Hepatocytes are considered to be the predominant source of alpha1-antitrypsin (AAT), the major antiprotease in human plasma. The development of emphysema in the hereditary PiZ AAT deficiency state suggests that inhibition of leukocyte elastase in the lung is a major function of this protein. In addition, patients with AAT deficiency are at increased risk for developing cholestasis in infancy and chronic liver disease as adults. The mechanism for hepatic cell injury, however, is not understood. Transgenic mice that express the normal human AAT gene demonstrate abundant AAT in hepatocytes and specific cell types of numerous nonhepatic tissues. Immunoperoxidase techniques have previously disclosed AAT in many of the cell types seen in transgenic mice; however, the issue of local synthesis vs. endocytosis in these cell types has remained unresolved. In this study, AAT mRNA was seen in a variety of tissues in the transgenic mouse. Immunoelectron microscopy of renal tubular and small intestinal epithelial cells in the transgenic mice demonstrated AAT within the cisternae of the rough endoplasmic reticulum, as in hepatocytes. These findings support the possibility of local synthesis in the various cell types. The results suggest that in addition to maintaining tissue integrity in the lung, the protease/antiprotease balance may have physiological functions in other organs as well.

Original languageEnglish (US)
Pages (from-to)26-36
Number of pages11
JournalJournal of Clinical Investigation
Volume82
Issue number1
StatePublished - 1988
Externally publishedYes

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Transgenic Mice
Hepatocytes
Protease Inhibitors
Lung
Leukocyte Elastase
Immunoelectron Microscopy
Rough Endoplasmic Reticulum
Cholestasis
Emphysema
Endocytosis
Immunoenzyme Techniques
Liver Diseases
Peptide Hydrolases
Chronic Disease
Epithelial Cells
Kidney
Messenger RNA
Wounds and Injuries
Genes
Proteins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Carlson, J. A., Rogers, B. B., Sifers, R. N., Hawkins, H. K., Finegold, M. J., & Woo, S. L. C. (1988). Multiple tissues express alpha1-antitrypsin in transgenic mice and man. Journal of Clinical Investigation, 82(1), 26-36.

Multiple tissues express alpha1-antitrypsin in transgenic mice and man. / Carlson, J. A.; Rogers, B. B.; Sifers, R. N.; Hawkins, H. K.; Finegold, M. J.; Woo, S. L C.

In: Journal of Clinical Investigation, Vol. 82, No. 1, 1988, p. 26-36.

Research output: Contribution to journalArticle

Carlson, JA, Rogers, BB, Sifers, RN, Hawkins, HK, Finegold, MJ & Woo, SLC 1988, 'Multiple tissues express alpha1-antitrypsin in transgenic mice and man', Journal of Clinical Investigation, vol. 82, no. 1, pp. 26-36.
Carlson JA, Rogers BB, Sifers RN, Hawkins HK, Finegold MJ, Woo SLC. Multiple tissues express alpha1-antitrypsin in transgenic mice and man. Journal of Clinical Investigation. 1988;82(1):26-36.
Carlson, J. A. ; Rogers, B. B. ; Sifers, R. N. ; Hawkins, H. K. ; Finegold, M. J. ; Woo, S. L C. / Multiple tissues express alpha1-antitrypsin in transgenic mice and man. In: Journal of Clinical Investigation. 1988 ; Vol. 82, No. 1. pp. 26-36.
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