Biosynthesis of Complement

Colten, Harvey R.

doi:10.1016/s0065-2776(08)60548-9

Cited by 166 publications

(57 citation statements)

References 123 publications

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“…Studies with fetal tissues demonstrated C5 production by a wide variety of tissues, suggesting that C5 is produced by a widely distributed cell type (33). Peritoneal macrophages synthesized C5 in the mouse (29), but evidence for active synthesis ofC5 in guinea pig peritoneal macrophages could not be demonstrated (34). In the human, Whaley reported that peripheral blood monocytes incorporated radiolabeled amino acids into a protein that precipitated with antiserum to C5 in Ouchterlony analysis (35), but other investigators could not detect C5 protein with the expected size and subunit composition (36) or C5 mRNA (Strunk, R. C., and F. S. Cole, unpublished observations) in these cells.…”

Section: Resultsmentioning

confidence: 99%

Pulmonary alveolar type II epithelial cells synthesize and secrete proteins of the classical and alternative complement pathways.

Strunk¹,

Eidlen²,

Mason³

1988

J. Clin. Invest.

262

137

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The serum complement system is a major mediator of inflammation reactions. Two of the complement proteins, the third (C3) and fifth (C5) components, are precursors of potent phlogistic molecules, C3a and CSa. C5a has potent chemotactic activity and plays an active role in pulmonary inflammation. We present evidence suggesting that several complement proteins, including C5, are synthesized locally in the lung in alveolar type II epithelial cells. Lung tissue from normal mice synthesized and secreted C5 protein similar to the C5 protein in mouse serum, whereas lung tissue from C5-deficient mice did not. Lung tissues from both normal and C5-deficient mice synthesized C3. Rat lung tissue synthesized and secreted C5, as well as C2, C4, C3, and factor B. Cultures of type II cells (95% type II cells, 5% macrophages) regularly synthesized all these proteins. In contrast, cultures of macrophages alone synthesized large amounts of C2 and factor B, and in some experiments C3 and C4, but never C5. The C5 synthesized by the rat cells was slightly larger than serum C5 (200 kD compared with 180 kD) and was not processed to the two-chain molecule seen in serum. Rat lung tissue and purified type II cells contained C5 mRNA with the same molecular mass as the C5 mRNA in rat liver and in mouse lung and liver. Human type II cells also synthesized C5, as well as C2, C4, C3, and factor B. Human pulmonary macrophages synthesized only C2, factor B, and, in some experiments, C3. Synthesis of complement proteins in cells that line the alveolar wall may provide a local source of these proteins for inflammatory responses in the lung. Local synthesis of complement proteins could be regulated independently of the synthesis in the liver.

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Section: Resultsmentioning

confidence: 99%

Pulmonary alveolar type II epithelial cells synthesize and secrete proteins of the classical and alternative complement pathways.

Strunk¹,

Eidlen²,

Mason³

1988

J. Clin. Invest.

262

137

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“…In this regard a,-antitrypsin, type Z , has been shown to be deficient in sialic acid, both in the serum (2,7) and in the liver (9,20). (3) Since no newly synthesized intracellular a,-antitrypsin was detected even in normal liver, it is probable that the newly synthesized normal protein is rapidly secreted, as has been demonstrated for the synthesis and secretion of albumin (21) and complement (6). (4) A less likely possibility is that the Z protein may be heterogeneous, some accumulating and some being Previous studies in vivo have demonstrated a,-antitrypsin in hepatocytes by immunofluorescence (23).…”

Section: Materials and Methods A-antitrypsin Quantitation A N D Typingmentioning

confidence: 97%

Liver in α1-Antitrypsin Deficiency: Morphologic Observations and in Vitro Synthesis of α1-Antitrypsin

Bhan¹,

Grand²,

Colten³

et al. 1976

Pediatr Res

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Extract disease (3). An increased incidence of lung (16) and liver disease (4,In an effort to characterize the hepatic abnormality in patients with a,-antitrypsin deficiency, three unrelated children with the disorder (Pi types Z Z and S Z ) , two heterozygous parents ( P i type MZ), and three normal subjects ( P i type M M ) were studied. As expected, the livers of the ZZ-and SZ-deficient subjects showed abnormal accumulation of a,-antitrypsin in the cisternae of the rough endoplasmic reticulum as judged by immunofluorescent and electron microscopic studies. Their parents ( M Z phenotype) demonstrated identical although less extensive hepatic abnormalities. Short term cultures of liver tissue in the presence of radiolabeled amino acids showed both synthesis and release of a,-antitrypsin in normal control subjects and in the patients with the Z protein.Radiolabeled intracellular a,-antitrypsin could not be found. These studies demonstrate synthesis of a,-antitrypsin by the livers of normal and genetically deficient subjects vitro, and suggest several possible mechanisms for a,-antitrypsin deficiency.5) may occur in persons with intermediate levels of a,-antitrypsin.Hepatocytes from patients with severe a,-antitrypsin deficiency contain abundant a,-antitrypsin protein (23), and it has been postulated that the low serum level in these subjects is associated with a failure of release of the protein from hepatic ribosomes. Although the liver is thought to be the only site of synthesis of this protein (23), no studies in vitro of a,-antitrypsin synthesis have been reported.The present investigation was undertaken to examine the synthesis of a,-antitrypsin and its release from the liver in patients with Z Z and S Z deficiency, the M Z phenotype, and in normal subjects (Pi type MM). MATERIALS AND METHODS a,-ANTITRYPSIN QUANTITATION A N D TYPINGThe concentration of a,-antitrypsin in serum was determined Speculation both by an automated nephelometric method (22) and by electroimmunoassay (17) using monospecific antiserum to a,-antitrypStudies in vitro of the synthesis and release of a,-antitrypsin, as sin obtained from Atlantic Antibodies (28). Genetic typing was shown in the present investigation, may reveal the molecular basis of performed by immunofixation with this antiserum after agarose this genetic disorder.gel electrophoresis at pH 8.6 (15). as well as crossed immunoelectrophoresis after starch gel electrophoresis at pH 4.95 (12).a,-Antitrypsin is a 50,000-dalton glycoprotein that accounts for about 90% of the total trypsin inhibitory capacity of normal human serum. It is also a major extracellular inhibitor of other proteolytic enrymes such as plasmin, elastase, collagenase, chymotrypsin, thrombin, and leukocyte proteases (18). Individuals homozygous for P i V h u s have 5 15% of the normal a,-antitrypsin level and heterozygotes for P i h n d PiS have about 30% of the normal concentration (10). An allele with no detectablc product (Pi-) has also been described (25) and the heterozygotes for this gene have serum ...

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“…For a historical perspective, the reader is referred to an excellent review by Colten (1976). Many studies have clearly demonstrated that the liver is the primary site of synthesis of most of the complement components (reviewed in Colten, 1976;Perlmutter and Colten, 1986;Burger, 1988;Cole and Colten, 1988;DiScipio et ai, 1988), with hepatocytes producing over 90% of serum complement (Alper and Rosen, 1976). Hepatocytes synthesize all the components, with the possible exception of factor D, the receptors for C3 ligands (CR1-CR4), and properdin (Table 2).…”

Section: Tissue Sites Of Complement Synthesismentioning

confidence: 99%

Complement Biosynthesis in the Central Nervous System

Barnum

1995

Critical Reviews in Oral Biology & Medicine

187

103

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ABSTRACT:Complement is an important effector arm of the human immune response. Binding of proteolytic fragments derived from activation of complement by specific receptors leads to responses as diverse as inflammation, opsonization, and B-cell activation. The importance of characterizing the expression and regulation of complement in the CNS is highlighted by growing evidence that complement plays a significant role in the pathogenesis of a variety of neurological diseases, such as multiple sclerosis and Alzheimer's disease. \n vitro studies have demonstrated that astrocytes, the predominant glial cell type in the brain, are capable of expressing or producing a majority of the components of the complement system. Expression of many complement proteins synthesized by astrocytes is regulated by both pro-and anti-inflammatory cytokines, many of which are also produced by several cell types in the CNS. In addition to astrocytes, ependymal cells, endothelial cells, microglia, and neurons have recently been shown to synthesize various complement proteins or express complement receptors on their cell surfaces. Together, these studies demonstrate that several cell types throughout the brain have the potential to express complement and, in many cases, increase expression in response to mediators of the acute phase response. These studies suggest that complement may play a greater role in CNS immune responses than previously thought, and pave the way for better understanding of the dynamics of complement expression and regulation in vivo. Such understanding may lead to therapeutic manipulation of complement host defense functions in a variety of inflammatory and degenerative diseases in the CNS.

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Biosynthesis of Complement

Cited by 166 publications

References 123 publications

Pulmonary alveolar type II epithelial cells synthesize and secrete proteins of the classical and alternative complement pathways.

Pulmonary alveolar type II epithelial cells synthesize and secrete proteins of the classical and alternative complement pathways.

Liver in α1-Antitrypsin Deficiency: Morphologic Observations and in Vitro Synthesis of α1-Antitrypsin

Complement Biosynthesis in the Central Nervous System

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