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PubMed1981

Regulation of protein synthesis: translational control by procollagen-derived fragments.

Previous studies have shown that a type I procollagen-derived peptide, called pN alpha 1(I)-Col 1, selectively inhibits collagen synthesis by fibroblasts in culture and the translation of procollagen mRNA in a rabbit reticulocyte lysate system. We prepared the 10,700-dalton peptide from dermatosparactic calf skin, which contained high levels of incompletely processed type I procollagen, by collagenase digestion. Time-course and dose-response studies showed that the peptide specifically inhibited the translation of procollagen mRNA in preparations of human fibroblast RNA while not affecting the translation of globin mRNA or of other messenger RNAs in fibroblast RNA. After reduction and alkylation, the peptide lost its specificity but became a nonspecific inhibitor of translation. Enzymatic cleavage enabled us to localize the nonspecific activity to a short sequence -Pro-Thr-Asp-Glu, an assignment confirmed by peptide synthesis. Using pactamycin, a specific inhibitor of translational initiation, we showed that the intact peptide acts on procollagen mRNA translation by inhibition of polypeptide chain elongation or termination, or both, whereas the nonspecific inhibitory activity of the unfolded peptide and its derivatives can be attributed to an inhibition of chain initiation. Although the native peptide may function in feedback regulation of collagen synthesis, the physiological role of the lower molecular weight fragments, if any, is uncertain.

Amino Acid Sequence↗

PubMed1985

Human alpha 1(III) and alpha 2(V) procollagen genes are located on the long arm of chromosome 2.

The multigene procollagen family encodes probably greater than 20 genetically distinct but structurally related polypeptide chains. Recent characterization of human procollagen clones has allowed determination of functional domains within the proteins, genomic organization, and chromosomal location. Previously, we assigned the coordinately expressed type I genes (alpha 1 and alpha 2) to chromosomes 17 and 7, respectively, and now other investigators have mapped the type II gene to chromosome 12 [Strom, C. M., Eddy, R. L. & Shows, T. B. (1984) Somatic Cell Genet. 10, 651-655]. Recently, we isolated cDNA clones encoding the fourth interstitial procollagen, type III, and the alpha 2 chain of the type V cytoskeletal components. To determine whether these genes were clustered with alpha 1(I), alpha 2(I), or alpha 1(II) or were further dispersed in the genome, in situ hybridization of the alpha 1(III) and alpha 2(V) probes to metaphase chromosomes was carried out. Here we report a fourth autosome with procollagen gene loci but the first cytological evidence for linkage. By using normal and translocated cell lines, our results show that both the alpha 1(III) and alpha 2(V) procollagen genes map to the q24.3----q31 region of chromosome 2.

Chromosome Mapping↗

PubMed1991

Stop codon in the procollagen II gene (COL2A1) in a family with the Stickler syndrome (arthro-ophthalmopathy).

Linkage analysis with restriction fragment length polymorphisms for the gene for type II procollagen (COL2A1) was carried out in a family with the Stickler syndrome, or arthro-ophthalmopathy, an autosomal dominant disorder that affects the eyes, ears, joints, and skeleton. The analysis demonstrated linkage of the disease and COL2A1 with a logarithm-of-odds score of 1.51 at zero recombination. A newly developed procedure for preparing cosmid clones was employed to isolate the allele for type II procollagen that was linked to the disease. Analysis of over 7000 nucleotides of the gene revealed a single base mutation that altered a CG dinucleotide and converted the codon CGA for arginine at amino acid position alpha 1-732 to TGA, a stop codon. From previous work on procollagen biosynthesis, it is apparent that the truncated polypeptide synthesized from an allele with a stop codon at alpha 1-732 cannot participate in the assembly of type II procollagen, and therefore that the mutation would decrease synthesis of type II procollagen. It was not apparent, however, why the mutation produced marked changes in the eye, which contains only small amounts of type II collagen, but relatively mild effects on the many cartilaginous structures of the body that are rich in the same protein.

Base Sequence↗

PubMed2005

Domains and maturation processes that regulate the activity of ADAMTS-2, a metalloproteinase cleaving the aminopropeptide of fibrillar procollagens types I-III and V.

Processing of fibrillar collagens is required to generate collagen monomers able to self-assemble into elongated and cylindrical collagen fibrils. ADAMTS-2 belongs to the "A disintegrin and metalloproteinase with thrombospondin type 1 motifs" (ADAMTS) family. It is responsible for most of the processing of the aminopropeptide of type I procollagen in the skin, and it also cleaves type II and type III procollagens. ADAMTS are complex secreted enzymes that are implicated in various physiological and pathological processes. Despite accumulating evidence indicating that their activity is regulated by ancillary domains, additional information is required for a better understanding of the specific function of each domain. We have generated 17 different recombinant forms of bovine ADAMTS-2 and characterized their processing, activity, and cleavage specificity. The results indicated the following: (i) activation of the ADAMTS-2 zymogen involves several cleavages, by proprotein convertases and C-terminal processing, and generates at least seven distinct processed forms; (ii) the C-terminal domain negatively regulates enzyme activity, whereas two thrombospondin type 1 repeats are enhancer regulators; (iii) the 104-kDa form displays the highest aminoprocollagen peptidase activity on procollagen type I; (iv) ADAMTS-2 processes the aminopropeptide of alpha1 type V procollagen homotrimer at the end of the variable domain; and (v) the cleaved sequence (PA) is different from the previously described sites ((P/A)Q) for ADAMTS-2, redefining its cleavage specificity. This finding and the existence of multiple processed forms of ADAMTS-2 strongly suggest that ADAMTS-2 may be involved in function(s) other than processing of fibrillar procollagen types I-III.

ADAM Proteins↗

PubMed2000

Hsp47: a molecular chaperone that interacts with and stabilizes correctly-folded procollagen.

Hsp47 is a heat-shock protein that interacts transiently with procollagen during its folding, assembly and transport from the endoplasmic reticulum (ER) of mammalian cells. It has been suggested to carry out a diverse range of functions, such as acting as a molecular chaperone facilitating the folding and assembly of procollagen molecules, retaining unfolded molecules within the ER, and assisting the transport of correctly folded molecules from the ER to the Golgi apparatus. Here we define the substrate recognition of Hsp47, demonstrating that it interacts preferentially with triple-helical procollagen molecules. The association of Hsp47 with procollagen coincides with the formation of a collagen triple helix. This demonstrates that Hsp47's role in procollagen folding and assembly is distinct from that of prolyl 4-hydroxylase. These results indicate that Hsp47 acts as a novel molecular chaperone, potentially stabilizing the correctly folded collagen helix from heat denaturation before its transport from the ER.

Animals↗

PubMed1980

Procollagen mRNA metabolism during the fibroblast cell cycle and its synthesis in transformed cells.

Procollagen mRNA was isolated from mouse embryos and used for the synthesis of a highly labelled cDNA probe complementary to collagen mRNA. This probe was used for the investigation of procollagen mRNA metabolism during the cell cycle of 3T6 mouse embryo fibroblasts in culture. Titration hybridization experiments revealed that procollagen mRNA was present throughout the cell cycle following stumulation of confluent monolayers. Procollagen mRNA levels of sparse cultures appeared similar to those of unstimulated monolayers. The fluctuating levels of collagen synthesis during the cell cycle can be ascribed to changes in the amount of collagen mRNA present. In mouse sarcoma virus transformed 3T3 cells only 20--30% of the amount of procollagen mRNA in 3T3 cells is present indicating that the decline in collagen synthesis is due to mRNA availability.

Animals↗

PubMed2001

Inhibitory effect of the angiotensin converting enzyme inhibitors captopril and enalapril on the conversion of procollagen to collagen.

OBJECTIVE AND DESIGN: Angiotensin converting enzyme inhibitors are reported to inhibit the collagen accumulation involved in left ventricular hypertrophy. We tested the effect of captopril and enalapril on the conversion of procollagen to collagen in short-term tissue cultures in order to study the possible mechanisms by which the antifibrotic effect of this group of inhibitors takes place. METHODS: We employed short-term cartilage and tendon tissue cultures to monitor the conversion of procollagen to collagen. After pulse-labelling with [14C]-proline, the cultures were incubated further with the test compounds in different concentrations for a 180 min chase period. The reaction was stopped and radioactive collagenous peptides were analysed by gel electrophoresis. The amounts of collagenous proalpha and alpha chains were estimated, and the inhibition of procollagen to collagen conversion was calculated relative to 0 min control (100% inhibition) and 180 min control (0% inhibition) samples. RESULTS: Inhibition (50%) was obtained with 7 mmol/l captopril and 22 mmol/l enalapril in the cartilage cultures. Both compounds seemed to inhibit the conversion in clearly lower concentrations in tendon cultures, 4 mmol/l and 7 mmol/l, respectively, were sufficient for 50% inhibition. Angiotensin I, II, saralasin and bradykinin did not have any effect on conversion at 3.5, 9, 2 and 4 mmol/l concentrations, respectively. CONCLUSION: The peptidase inhibitors captopril and enalapril are able to inhibit the conversion of procollagen to collagen, which is a proteolytic process, possibly by inhibiting the specific procollagen proteases. Whether this phenomenon is involved in the antifibrotic property of angiotensin converting enzyme inhibitors warrants further study, as does the question of whether new antifibrotic agents could be developed on this basis.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1986

Progressive nodular fibrosis of the skin: altered procollagen and collagenase expression by cultured fibroblasts.

A 33-year-old man presented with a spontaneous progressive cutaneous tumor-like fibrosis involving the right leg and buttock. Histologically the deep dermis was composed of numerous fibroblasts and dense bands of collagen, suggesting that the lesion might be related to an abnormality in collagen metabolism. Fibroblast cultures were established from the affected and normal-appearing skin. The growth rate of the lesional cells was essentially equal to that of control cells. The synthesis of procollagen was approximately 3.5-fold increased in the cells derived from the nodules when compared with control fibroblasts (p less than 0.001). The increase in procollagen synthesis was reflected by an approximate 6-fold increase in both type I and type III procollagen mRNA abundance in the lesional fibroblasts (p less than 0.001), thus suggesting an aberration in the pretranslational level of procollagen gene expression. In contrast, the synthesis of collagenase, the enzyme required for the initiation of collagen degradation, was decreased to approximately 25% of control values (p less than 0.0025), although the enzyme was catalytically normal. The data indicate that these cells are characterized by an increased synthesis of procollagen and decreased synthesis of collagenase, 2 phenotypic characteristics that could account pathophysiologically for the lesions. The unusual reciprocal nature of these biochemical parameters in 2 proteins important in connective tissue homeostasis suggests that this progressive tumor-like condition may have resulted from the expansion of a clonal population of cells.

Adult↗

PubMed1979

Amino acid sequence of the aminoterminal segment of dermatosparactic calf-skin procollagen type I.

The N-terminal procollagen peptide of the pN alpha 1(I) chain from dermatosparactic calf skin contains 139 amino acid residues. For the determination of the amino acid sequence the procollagen peptide was treated with pyroglutamate aminopeptidase, protease from Staphylococcus aureus V8 and trypsin. The fragments obtained were separated by molecular sieve and ion-exchange chromatography and submitted to automated Edman degradation. The procollagen peptide consists of three segments, an N-terminal globular domain which contains all the cysteine residues and most of the hydrophobic residues present in the entire peptide, a triple helical part with a relatively high content of proline and hydroxyproline, and a short nonhelical region which forms the connection to the nonhelical region of the alpha 1(I) chain and which contains the proline-glutamine bond specifically split by the N-terminal procollagen peptidase during conversion of procollagen to collagen.

Amino Acid Sequence↗

PubMed1985

Biosynthesis and in vitro translation of type IV procollagens.

The present paper describes how epithelial cells, cultured from bovine anterior lens capsule explants, synthesize and secrete procollagen type IV polypeptide chains alpha 1(IV) and alpha 2(IV). Metabolic labeling of these cells with [14C]proline for different time intervals and subsequent analysis by SDS/polyacrylamide gel electrophoresis revealed the presence of two polypeptide chains with apparent molecular masses of 180 kDa and 170 kDa. The procollagens were bacterial-collagenase-sensitive and were specifically immunoprecipitated by antibodies raised against the 7S domain of type IV collagen. Type IV procollagen poly(A)-rich RNA was isolated from cultured lens capsule cells and translated in a reticulocyte lysate cell-free system. Two polypeptides with apparent molecular masses of 152 kDa and 145 kDa were identified as procollagen type IV unmodified chains by gel electrophoresis, collagenase digestion and specific immunoprecipitation. During experiments in which cells were labeled in the presence of alpha, alpha'-bipyridyl, type IV procollagen appeared as one major band comigrating with a 145 kDa polypeptide on SDS-gel electrophoresis.

Animals↗

PubMed2006

Procollagen 1 - a marker of fibroblastic and fibrohistiocytic skin tumors.

BACKGROUND: When dealing with tumors of presumed fibroblastic or fibrohistiocytic origin, immunohistochemistry is traditionally done to exclude a tumor of non-fibroblastic or non-fibrohistiocytic nature, because a reliable marker of fibroblastic or fibrohistiocytic cell origin is still to be introduced. This study investigates whether procollagen 1 is a useful marker of skin tumors composed of cells derived from fibroblasts or fibrohistiocytes. MATERIALS AND METHODS: Twenty-nine different types of skin tumors, including tumors composed of spindle cells as well as some additional epithelial and melanocytic tumors, were stained immunohistochemically with antibodies against procollagen 1. The total number of cases tested was 154. RESULTS: Tumors composed of cells of fibroblastic or fibrohistiocytic origin in general showed a high expression of procollagen 1, whereas tumors composed of non-fibroblastic cells in general showed no expression. However, there were a few exceptions, e.g., leiomyosarcoma and desmoplastic melanoma. CONCLUSIONS: The study suggests that immunohistochemical staining for procollagen 1 is a valuable marker for skin tumors composed of spindle cells derived from fibroblasts or fibrohistiocytes. However, in cases of spindle cell tumors with a morphology suggesting malignancy, it is recommended to use a panel of antibodies, which besides procollagen 1 includes markers such as S100, CD68, CD34, h-caldesmon, and pancytokeratin.

Biomarkers, Tumor↗

PubMed1998

Localisation and semiquantitative assessment of hepatic procollagen mRNA in primary biliary cirrhosis.

BACKGROUND: Chronic liver disease is characterised by excessive deposition of collagen and other extracellular matrix proteins, produced mainly, but not exclusively, by activated hepatic stellate cells in the perisinusoidal space. In primary biliary cirrhosis (PBC) fibrosis is concentrated mainly around the portal tracts. AIMS: To examine the hypothesis that, in addition to hepatic stellate cells, portal tract fibroblasts might play a significant role in the deposition of collagen in PBC. METHODS: Fifty liver biopsy specimens from patients with PBC were studied. An in situ hybridisation technique was adapted to localise and measure semiquantitatively type I procollagen mRNA in formalin fixed, paraffin wax embedded sections, using an 35S labelled cRNA probe specific for the alpha 1 chain of rat type I procollagen. Hepatic fibrogenic activity was also assessed using serum type III procollagen peptide (PIIINP). RESULTS: In PBC, type I procollagen gene expression was significantly increased. Signal was localised mainly in and around inflamed portal tracts, to cells which had the appearances of portal fibroblasts. Signal activity in these cells correlated with the degree of portal fibrosis and inflammation and also with serum PIIINP concentrations. CONCLUSIONS: Results are consistent with the hypothesis that the excessive extracellular matrix, deposited within the liver in PBC, is synthesised not only by hepatic stellate cells but also by portal tract fibroblasts. The semiquantitative assessment of procollagen mRNA in liver biopsy specimens may provide a useful method of evaluating the rate of synthesis of collagen and therefore disease activity in patients with PBC.

Biomarkers↗

PubMed1989

Hyaluronan and type III procollagen peptide concentrations in bronchoalveolar lavage fluid in idiopathic pulmonary fibrosis.

The connective tissue components hyaluronan (hyaluronic acid) and type III procollagen peptide were measured in bronchoalveolar lavage fluid in 22 patients with idiopathic pulmonary fibrosis and 21 healthy control subjects. The patients with idiopathic pulmonary fibrosis had higher concentrations of hyaluronan (median 46 micrograms/l) and type III procollagen peptide (median 0.45 micrograms/l) than the healthy controls (9 and less than 0.02 micrograms/l; p less than 0.001). The patients had normal serum concentrations of hyaluronan and of the procollagen peptide, and albumin concentrations in lavage fluid similar to those of the control subjects. Neutrophil and lymphocyte counts in lavage fluid were increased on average 10 and two fold respectively in the patients with idiopathic pulmonary fibrosis and both correlated with the amount of hyaluronan recovered (p less than 0.05). An inverse correlation was seen between the transfer factor for carbon monoxide and hyaluronan concentrations in lavage fluid in the patients (p less than 0.05). Deterioration in lung function and radiographic progression were seen over six months in 12 of the patients. These patients had higher lavage fluid concentrations of hyaluronan and type III procollagen peptide than the patients whose disease was stable (p less than 0.01). Increased synthesis of hyaluronan and type III procollagen peptide in lung parenchyma may reflect activation or proliferation (or both) of pulmonary fibroblasts in idiopathic pulmonary fibrosis and seems to be linked to the severity and activity of the lung disease.

Adult↗

PubMed2004

Effects of jump training on procollagen alpha(1)(i) mRNA expression and its relationship with muscle collagen concentration.

The aim of this study was to examine the effects of a prolonged high-intensity exercise, jumping, on procollagen alpha(1)(I) mRNA level and collagen concentration in different muscles of trained (T) and control (C) rabbits. Procollagen alpha(1)(I) mRNA expression was much higher (2.8 to 23.5 times) in semimembranosus proprius (SMP), a slow-twitch oxidative muscle, than in extensor digitorum longus (EDL), rectus femoris (RF), and psoas major (Psoas) muscles, both fast-twitch mixed and glycolytic, whatever group was considered (p < 0.001). Procollagen alpha(1)(I) mRNA level also decreased significantly between 50 and 140 days in all muscles (0.001< p < 0.01). However, mRNA levels were 16 to 97% greater at 140 days in all muscles of T animals compared to C ones (0.01< p <0.05). Collagen concentrations of EDL and RF muscles were also higher (14 to 19%) in T than in C rabbits at 90 and 140 days (0.001 < p < 0.05). In the whole sample, collagen concentration was negatively associated with the procollagen alpha(1)(I) mRNA level in EDL and RF muscles (- 0.49 < r < (- 0.44, p < 0.05), while being positively related to mRNA expression in SMP and Psoas muscles (0.65 < r < 0.85, p < 0.01). It is concluded that jump training clearly restricts the decrease of procollagen (I) mRNA level and probably affects collagen synthesis level. In trained rabbit muscles, the maintenance of a better synthesis level could partly explain the higher collagen concentrations found in EDL and RF at 140 days. Nevertheless, the collagen degradation process seems to play the main role in the increase of total collagen concentration with age in EDL and RF muscles.

Age Factors↗

PubMed1990

Bleomycin and cyclophosphamide increase pulmonary type IV procollagen mRNA in mice.

Constant 7-day subcutaneous infusion of bleomycin (100 mg/kg) induces pulmonary fibrosis in C57Bl/6N mice, whereas BALB/cN mice are relatively resistant. In contrast, cyclophosphamide (200 mg/kg, ip) induces fibrosis in BALB/cN mice, whereas C57Bl/6N mice are resistant. The effect of these drugs on the pulmonary levels of mRNA encoding the major basement membrane components, laminin and type IV collagen, relative to poly (A+)RNA was determined in both C57Bl/6N and BALB/cN mice. In the sensitive C57Bl/6N mice, bleomycin increased alpha 1IV and alpha 2IV procollagen mRNA/poly (A+)RNA twofold in the absence of increases in laminin A, B1, and B2 mRNA/poly (A+)RNA. In the relatively resistant BALB/cN mice, bleomycin did not alter alpha 1IV procollagen mRNA/poly (A+)RNA and only transiently increased laminin A, B1, B2, and alpha 2IV procollagen mRNA/poly (A+)RNA. Similarly, cyclophosphamide increased alpha 1IV and alpha 2IV procollagen mRNA/poly (A+)RNA twofold in the sensitive BALB/cN mice and not in C57Bl/6N mice. Laminin mRNAs/poly (A+)RNA were not increased by cyclophosphamide in either strain. Thus, in these models, pulmonary fibrosis is preceded by a coordinate increase in steady-state levels of mRNA encoding basement membrane procollagen but is not associated with an increase in laminin gene expression.

Animals↗

PubMed1996

Procollagen type I carboxyterminal extension peptide in serum: a reliable marker of bone metastatic disease in newly diagnosed prostate cancer?

OBJECTIVE: This study evaluates the accuracy of type I procollagen, a bone matrix glycoprotein, and prostate-specific antigen (PSA) as markers for predicting the results of radionuclide bone scan in newly diagnosed, previously untreated patients with prostate cancer. METHODS: 74 patients underwent serum PSA and procollagen determination using specific antibodies. A staging radionuclide bone scan was then performed; patients with positive bone scan were submitted to x-rays of the suspicious zones. Then, we calculated sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of procollagen and PSA in the detection of bone metastases. RESULTS: Procollagen alone had 83.3% sensitivity, 96% specificity, 90.9% positive predictive value, 92.3% negative predictive value and 91.9% overall accuracy. PSA alone had 70.1% sensitivity, 86% specificity, 70.8% positive predictive value, 86% negative predictive value and 81.1% overall accuracy. CONCLUSIONS: According to our data, we no longer perform a staging radionuclide bone scan in patients with PSA < 20 ng/ml and normal procollagen level, diminishing the number of radionuclide bone scans and increasing the overall net savings for the health care system.

Aged↗

PubMed1995

Histomorphometric and biochemical correlates of arterial procollagen gene expression during vascular repair after experimental angioplasty.

BACKGROUND: To determine the transcriptional, biochemical, and histomorphometric correlates of neointimal procollagen accumulation during arterial repair after balloon angioplasty of atherogenic vessels, rabbit iliac artery collagen content and the induction of alpha 1(I) and alpha 1(III) procollagen mRNA were assessed in normal vessels and at 2, 7, and 30 days after angioplasty. METHODS AND RESULTS: Quantitative iliac artery histomorphometric neointimal collagen analysis was performed using a specific picrosirius red stain under polarized light. Arterial cross-sectional area reduction, total cellularity, and vascular smooth muscle cell density (per 10(4) mu2 of neointima) were quantified in routine and immunohistochemically stained sections (alpha-actin and RAM-11), from which biochemical concentrations of tissue protein, RNA, and DNA were also measured. Collagen comprised 0.23 +/- 0.1 mg/mg of total protein in the normal vessel wall and did not increase in vessels studied 2 and 7 days after angioplasty (0.26 +/- 0.06, 0.28 +/- 0.05 mg/mg of protein, P = NS). By 30 days after angioplasty, > 50% of the protein concentration was collagen (0.55 +/- 0.11 mg/mg of protein, P = .02). Collagen-positive histological staining also increased significantly from 17 +/- 2% of the neointima at day 2 to 32 +/- 5% by day 30 (P = .01). The transcript regulatory signal for alpha 1(I) procollagen mRNA was induced 2 days after angioplasty, peaking at 7 days for both alpha 1(I) and alpha 1(III), and returning to control levels 30 days after angioplasty. A significant luminal cross-sectional area reduction of the arterial wall was confirmed both by angiography and histomorphometry (P = .01). This was not associated with a significant change in alpha-actin (+) vascular smooth muscle cell density (38 +/- 7 nuclei per 10(4) mu2 at day 2 and at day 30) or tissue DNA concentration (P = NS). CONCLUSIONS: We conclude that procollagen genes are transcriptionally activated early (2 to 7 days) after angioplasty vessel injury and that collagen subsequently constitutes a major biochemical and histological component of the proliferative neointima by 30 days after angioplasty. Alterations in pathways regulating procollagen metabolism may also contribute to the accumulation of extracellular matrix and growth of the neointima in the late repair phase after vessel wall injury.

Angioplasty, Balloon↗

PubMed1999

Type III and type I procollagen markers in fibrosing alveolitis.

Deposition of types I and III collagen is a typical feature in the development of pulmonary fibrosis. We assessed the propeptides of these procollagens as prognostic markers in 18 patients with fibrosing alveolitis. We analyzed the amino-terminal propeptide of type III procollagen (PIIINP) and the carboxy-terminal propeptide of type I procollagen (PICP) from samples of bronchoalveolar lavage fluid (BALF) and serum, and also estimated their concentrations in epithelial lining fluid (ELF) by the urea method. The level of PIIINP in serum (p < 0.05), BALF (p < 0.05), and ELF (p < 0.05), and the levels of PICP in BALF (p < 0.001) and ELF (p < 0.001) but not in serum, were significantly increased in the patients with fibrosing alveolitis as compared with 17 controls who had been investigated for minor respiratory symptoms. In the BALF and ELF of patients with fibrosing alveolitis, PICP but not PIIINP had significant negative correlations with the specific diffusion coefficient for carbon monoxide (DLCO/ VA). The amino-terminal propeptide of type III procollagen and the carboxy-terminal propeptide of type I procollagen in BALF correlated significantly with one another. During the follow-up period of 6 yr, seven of the 18 patients with fibrosing alveolitis died of the disease, 3 others died of malignancy, and one patient died from an unknown cause. DLCO (p < 0.05) differed significantly between the surviving patients and those who died of fibrosing alveolitis, and detectable PIIINP in BALF predicted death from fibrosing alveolitis (p = 0.05). In conclusion, these results show that PIIINP in BALF, ELF, and serum, and PICP in BALF and ELF, are increased in patients with fibrosing alveolitis. A high level of PICP in BALF, and especially in ELF, suggests a chronic process and increased synthesis of type I collagen in the lungs, whereas PIIINP in BALF and ELF suggests active disease and a poor prognosis.

Biomarkers↗