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Free access | 10.1172/JCI109297

Some Effects of the Administration of Endotoxin in Mice: SPECIFIC CLEAVAGE OF SERUM ALBUMIN BY AN ACID PROTEASE AND THE GENERATION OF AMYLOID SERUM COMPONENT

Peter D. Gorevic, Yoram Levo, Prem C. Chatpar, Blas Frangione, and E. C. Franklin

Department of Medicine, Irvington House Institute, New York 10016

Department of Pathology, Irvington House Institute, New York 10016

Rheumatic Diseases Study Group, Irvington House Institute, New York 10016

New York University Medical Center, New York 10016

Find articles by Gorevic, P. in: JCI | PubMed | Google Scholar

Department of Medicine, Irvington House Institute, New York 10016

Department of Pathology, Irvington House Institute, New York 10016

Rheumatic Diseases Study Group, Irvington House Institute, New York 10016

New York University Medical Center, New York 10016

Find articles by Levo, Y. in: JCI | PubMed | Google Scholar

Department of Medicine, Irvington House Institute, New York 10016

Department of Pathology, Irvington House Institute, New York 10016

Rheumatic Diseases Study Group, Irvington House Institute, New York 10016

New York University Medical Center, New York 10016

Find articles by Chatpar, P. in: JCI | PubMed | Google Scholar

Department of Medicine, Irvington House Institute, New York 10016

Department of Pathology, Irvington House Institute, New York 10016

Rheumatic Diseases Study Group, Irvington House Institute, New York 10016

New York University Medical Center, New York 10016

Find articles by Frangione, B. in: JCI | PubMed | Google Scholar

Department of Medicine, Irvington House Institute, New York 10016

Department of Pathology, Irvington House Institute, New York 10016

Rheumatic Diseases Study Group, Irvington House Institute, New York 10016

New York University Medical Center, New York 10016

Find articles by Franklin, E. in: JCI | PubMed | Google Scholar

Published February 1, 1979 - More info

Published in Volume 63, Issue 2 on February 1, 1979
J Clin Invest. 1979;63(2):254–261. https://doi.org/10.1172/JCI109297.
© 1979 The American Society for Clinical Investigation
Published February 1, 1979 - Version history
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Abstract

Endotoxin has been shown to induce amyloidosis in mice and to result in the appearance in serum of large amounts of amyloidrelated protein (SAA). After injection of 300 μg lipopolysaccharide Escherichia coli, SAA behaves as an acute phase reactant with levels reaching a peak of >600 μg/ml at 18-22 h and returning to base line (<50 μg/ml) by 48 h in each of four strains tested; only the endotoxin-resistant C3H/HeJ strain showed a smaller response. Lesser, though significant, elevations were also found after subcutaneous injection of 25 mg of casein, bovine serum albumin, ovalbumin, or monomeric immunoglobulin G, whereas pyrogen-free human serum albumin/U. S. Pharmacopeia failed to raise SAA levels. SAA generation may thus be a result of endotoxin contamination of these protein preparations.

Also present in equivalent amounts in acidified serum from endotoxin-treated mice, but barely detectable in control sera, was a 3,000-dalton molecule whose amino acid sequence is identical to the amino terminal 24 residues of mouse albumin. The appearance of SAA and the amino terminal albumin fragment after endotoxin were unaffected by pretreatment with cobra venom factor, and equivalent levels were found in C5-deficient mice. Pretreatment with pepstatin in vivo, or before acidification in vitro, prevented the appearance of the albumin fragment but had no effect on the appearance of SAA, whereas leupeptin and antipain did not affect the appearance of either SAA or the albumin fragment. These studies suggest that the generation of SAA after endotoxin administration does not involve complement activation or intravascular proteolytic activity, whereas the liberation of a specific peptic-like cleavage product of albumin appears to be the consequence of an acid protease.

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