Studies of the In Vivo Behavior of Human C′3 in Normal Subjects and Patients (original) (raw)
Research Article Free access | 10.1172/JCI105691
Department of Medicine, Children's Hospital Medical Center, Boston, Massachusetts
Department of Medicine, Peter Bent Brigham Hospital, Boston, Massachusetts
Department of Medicine, Harvard Medical School, and the Blood Grouping Laboratory, Boston, Massachusetts
Department of Pediatrics, Harvard Medical School, and the Blood Grouping Laboratory, Boston, Massachusetts
‡
Recipient of a career development award (1-K3-AM-19, 650) from the U. S. Public Health Service.
Address requests for reprints to Dr. Chester A. Alper, The Blood Grouping Laboratory, 332 Longwood Avenue, Boston, Mass. 02115.
*
Received for publication 8 June 1965 and in revised form 3 August 1967.
Supported by grants from the U. S. Public Health Service (AM 05877, AM 00965, FR 00128, 8 MO 1-FR-31-05, and NB 03492) and The John A. Hartford Foundation. Reported partially at a sectional meeting of The American Society for Clinical Investigation, 2 May 1965.
Find articles by Alper, C. in:[JCI](/search/results?q=author.first%5Fname%3A%22Chester A.%22+author.last%5Fname%3A%22Alper%22&search%5Ftype=advanced) |PubMed |Google Scholar
Department of Medicine, Children's Hospital Medical Center, Boston, Massachusetts
Department of Medicine, Peter Bent Brigham Hospital, Boston, Massachusetts
Department of Medicine, Harvard Medical School, and the Blood Grouping Laboratory, Boston, Massachusetts
Department of Pediatrics, Harvard Medical School, and the Blood Grouping Laboratory, Boston, Massachusetts
‡
Recipient of a career development award (1-K3-AM-19, 650) from the U. S. Public Health Service.
Address requests for reprints to Dr. Chester A. Alper, The Blood Grouping Laboratory, 332 Longwood Avenue, Boston, Mass. 02115.
*
Received for publication 8 June 1965 and in revised form 3 August 1967.
Supported by grants from the U. S. Public Health Service (AM 05877, AM 00965, FR 00128, 8 MO 1-FR-31-05, and NB 03492) and The John A. Hartford Foundation. Reported partially at a sectional meeting of The American Society for Clinical Investigation, 2 May 1965.
Find articles by Rosen, F. in:[JCI](/search/results?q=author.first%5Fname%3A%22Fred S.%22+author.last%5Fname%3A%22Rosen%22&search%5Ftype=advanced) |PubMed |Google Scholar
Published December 1, 1967 -More info
Published December 1, 1967 -Version history
The metabolic behavior of C′3 labeled with radioactive iodine was investigated in 10 normal subjects and in 20 patients with diseases in which complement is thought to play a pathophysiological role. The mean fractional catabolic rate of C′3 in normal subjects was 2.3 ± 1.0% of the plasma pool per hr, whereas the fractional catabolic rate of C′3i, the inactive conversion product of C′3 produced by complement activation, was at least five times as great.
Increased catabolic rates were found in some patients with acute glomerulonephritis, systemic lupus erythematosus, idiopathic nephrotic syndrome of childhood, and progressive glomerulonephritis. Depressed synthesis was found in each of four studies of patients with progressive glomerulonephritis and seemed to be the major factor in the lowering of plasma C′3 concentrations regularly observed in patients with this disease. Of three patients with acute glomerulonephritis, synthesis rates of C′3 were markedly depressed in one subject, at the lower limit of normal in another, and entirely normal in the third. Increased extravascular: plasma pool ratios were observed in the studies of C′3i metabolism in a normal subject, and of C′3 metabolism in two of three patients with acute glomerulonephritis, in one of four patients with systemic lupus erythematosus, and in one patient with idiopathic nephrotic syndrome. The increased pool ratios are possibly compatible with tissue attachment of part of the injected C′3 or its conversion products.
No important abnormalities of metabolism were found in patients with acquired hemolytic anemia, paroxysmal nocturnal hemoglobinuria, hereditary angioneurotic edema, or rheumatoid arthritis.
By means of antigen-antibody crossed electrophoresis, C′3i could be demonstrated in the fresh plasma of three of eight patients who had acute glomerulonephritis. This finding was used as evidence for in vivo complement activation in this disease. Since C′3i was demonstrated only in plasma from patients with very low plasma concentrations whose onset of symptoms was very recent, there may be two phases in the metabolism of C′3: early complement activation with resultant increased catabolism and later depressed synthesis, both of which lead to lowered serum concentrations.
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