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Biomedical subjects

S Lindgren

Publications and source records attributed to S Lindgren.

At least 55 records · Page 3Linked to original sources
PubMed2000

Alpha1-antitrypsin deficiency may be a risk factor for duodenal ulcer in patients with Helicobacter pylori infection.

BACKGROUND: Most individuals with Helicobacter pylori infection in Western countries have no evidence of peptic ulcer disease (PUD). We therefore assessed the PiZ deficiency variant of the major plasma protease inhibitor alpha1-antitrypsin (alpha1AT) as a risk factor for PUD in H. pylori-infected individuals. METHODS: The cohort comprised 100 patients with endoscopically or surgically proven PUD (30 patients with duodenal ulcer (DU) and 70 patients with gastric ulcer (GU)) and 162 age- and sex-matched controls with PUD-negative endoscopic findings and no history of PUD. Plasma samples were screened for alpha1AT deficiency (PiZ) with an enzyme-linked immunosorbent assay (ELISA) and phenotyped by isoelectric focusing. H. pylori infection was evaluated with an IgG ELISA technique. RESULTS: Among the 262 patients 17 (6.5%) were positive for the PiZ alpha1AT deficiency, a frequency of the same magnitude as in the Swedish general population (4.7%). Of the PiZ carriers 76% (13 of 17) had H. pylori antibodies compared with 61% (151 of 245) of the non-PiZ carriers (NS). The prevalence of DU tended to be higher in H. pylori-positive PiZ carriers than in non-PiZ carriers (15.4%, 4 of 26 versus 0 of 4). Furthermore, among patients with DU a high PiZ allele frequency (13.3%, 4 of 30) was found compared with the general population (4.7%) (odds ratio (OR), 3.2; 95% confidence interval (CI), 1.09-8.94; P = 0.02). All DU patients carrying the PiZ allele were positive for H. pylori. In addition, four of five PiZ carriers with H. pylori infection and PUD had DU. CONCLUSIONS: The PiZ allele may be a contributing factor in the development of DU in H. pylori-positive individuals.

Duodenal Ulcer↗
PubMed2000

Increased presence of cells containing transforming growth factor alpha (TGF-alpha) in ulcerative colitis, both during active inflammation and in remission.

OBJECTIVE: Patients with extensive and long-standing ulcerative colitis have an increased risk of developing colorectal cancer and sub-epithelial fibrosis. The polypeptide transforming growth factor alpha (TGF-alpha) has mitogenic effects and it is believed that local overproduction may result in tumour formation and fibrosis. DESIGN: In the present study, we correlated the presence of TGF-alpha in ulcerative colitis with the degree of inflammation and with dysplasia. METHODS: Sixty two patients were investigated, 46 with ulcerative colitis (16 with active inflammation and 20 in remission, 10 with dysplasia of the colon), and 16 controls with normal colonoscopy and without a history of colitis. There were no overlaps between the subgroups. Tissue sections from colonic biopsies were examined and TGF-alpha was detected by immunohistochemistry. TGF-alpha-containing cells were characterized by double-staining with antibodies to eosinophil cationic protein (ECP). An antibody (EG2) recognizing eosinophils with an activated phenotype was also used. RESULTS: The median number of TGF-alpha-containing cells in the mucosa was 24 per mm2 (inter-quartile range 10-51) in controls, 186 per mm2 (73-245) in ulcerative colitis with active inflammation, 76 per mm2 (52-198) in remission, and 130 per mm2 (66-203) in areas of dysplasia. Double-staining for TGF-alpha and ECP revealed that most of the TGF-alpha-containing cells were eosinophils, and most had an activated phenotype as judged by staining with EG2. CONCLUSIONS: The presence of TGF-alpha-containing cells in colonic mucosa is increased both in active inflammation and during remission in ulcerative colitis. Dysplasia is not associated with any significant increase in TGF-alpha-containing cells. The majority of TGF-alpha-containing cells are eosinophils with an activated phenotype. TGF-alpha released from these cells could be important for the development of complications seen in ulcerative colitis, such as cancer and fibrosis.

Adult↗
PubMed2000

Serum antibodies to Helicobacter hepaticus and Helicobacter pylori in patients with chronic liver disease.

BACKGROUND: Bile tolerant helicobacter species such as H hepaticus and H bilis have frequently been reported to cause hepatitis in mice and other rodents. AIMS: To investigate the possible pathogenic role of these and other helicobacter species in chronic liver disease in humans. METHODS: Serum samples from 144 patients with various chronic liver diseases, 30 patients with primary sclerosing cholangitis (PSC), and 48 healthy blood donors were analysed for antibodies against H hepaticus murine strain CCUG 33637 and H pylori strain CCUG 17874. Cell surface proteins of H hepaticus were extracted by acid glycine buffer and used in an enzyme immunoassay (EIA) and immunoblot (IB). RESULTS: 56 of 144 (39%) patients with chronic liver diseases and six of 30 (20%) with PSC showed increased antibody concentrations in the H hepaticus EIA; in the H pylori EIA the numbers were 58% and 13% respectively. Compared with the healthy blood donors the antibody reactivity against the two helicobacter species was not increased (46% and 48% respectively). Patient serum samples retested by the H hepaticus EIA after absorption with sonicated H pylori cells remained positive in 12 of 37 (33%) serum samples. Distinct antibody reactivity to 55-65 kDa proteins was observed by H hepaticus IB, after the absorption step, and was considered specific for H hepaticus. These 12 serum samples were from patients with chronic alcoholic liver disease. CONCLUSIONS: Antibodies to H hepaticus, often cross reacting with H pylori, occur frequently in patients with chronic liver diseases, with no clear cut relation to specific diagnostic groups. The pathogenic significance of these findings is not known.

Adult↗
PubMed2000

Production and characterization of novel anti-prostate-specific antigen (PSA) monoclonal antibodies that do not detect internally cleaved Lys145-Lys146 inactive PSA.

BACKGROUND: The nature of free, uncomplexed prostate-specific antigen (PSA) in the circulation is still unknown. In this study, we developed novel anti-PSA antibodies using PSA produced by a metastasized cancer cell line, LNCaP, as an immunogen. METHODS: Hybridoma cell lines were screened with different methods that aimed at finding antibodies specific for the forms of free PSA produced by LNCaP cell line. Obtained antibodies were further studied for their characteristics related to previously characterized monoclonal antibodies. RESULTS: Numerous anti-PSA antibodies were obtained, of which four represented unique epitopes previously unrecognized by us. One free-PSA-specific antibody was bound to PSA on two distinct epitopes, and one antibody was bound to the carboxyl-terminal peptide of PSA. Two antibodies were found to bind to the peptide sequence adjacent to the internal cleavage site Lys145-Lys146. These antibodies failed to recognize internally cleaved PSA at Lys145-Lys146. We could not find anti-proPSA antibodies despite the fact that LNCaP PSA contained more than one-half of the zymogen form of PSA. CONCLUSIONS: We report, for the first time, novel anti-PSA antibodies that do not recognize internally cleaved PSA at Lys145-Lys146 and thus are specific for intact, unclipped PSA.

Amino Acid Sequence↗
PubMed1999

[Immune response and inflammation in Crohn disease. More detailed diagnostics and more specific drugs are soon to be available].

The chronic inflammation in Crohn's disease may be caused by aggressive response to bacterial antigens normal to the gut. Genetic and environmental factors modify the inflammatory response evoked by damage to the mucosal gut barrier. Genetic factors may also determine the subsequent course of chronic inflammation. Further elucidation of the pathogenesis might improve our understanding of the heterogenous nature of Crohn's disease, thus enabling the disease to be subtyped and individualised therapy directed primarily at down-regulation of helper T-cell-1 response to be developed.

Crohn Disease↗
PubMed1999

Effects of fibrillar C-terminal fragment of cleaved alpha1-antitrypsin on cholesterol homeostasis in HepG2 cells.

Amyloid fibrils of diverse origin are known to disturb vital cellular functions and induce cell death. In this study, the effects of amyloid fibrils from the C-terminal fragment (C-36) of cleaved alpha1-antitrypsin (AAT) on low-density lipoprotein (LDL) metabolism were investigated in HepG2 cells. Treatment of the cells with C-36 fibrils (10 micromol/L) enhanced 125I-LDL binding and uptake 10 to 15 times, and highly up-regulated levels of LDL receptor mRNA, as compared with control cells. Competition experiments using excess of unlabeled LDL and blockage experiments with a monoclonal LDL receptor antibody diminished or completely abolished the stimulatory effects of fibrils on LDL binding and LDL receptor mRNA levels, suggesting that fibrils act via the LDL receptor pathway. However, C-36 fibrils had no significant effect on [2-14C]acetate incorporation into cholesterol biosynthesis and cholesterol ester formation, but inhibited 125I-LDL degradation by 20% and reduced bile acid biosynthesis up to 48% in a dose-dependent manner. Preincubation of the cells with fibrils before the addition of LDL totally abolished the LDL inhibitory effect on unesterified cholesterol synthesis, further confirming the LDL receptors to be the target for C-36 fibrils. Moreover, the expression of sterol regulatory element binding protein-1 (SREBP-1) was found to increase twofold and more after 24 hours of incubation of the cells with several concentrations of C-36 fibrils. Our study suggests that the cytotoxicity of C-36 fibrils on HepG2 cells is associated with perturbed intracellular cholesterol homeostasis, induced through fibril-stimulated expression of the LDL receptors via the sterol-responsive element.

Acetates↗
PubMed1999

Atherogenic properties of human monocytes induced by the carboxyl terminal proteolytic fragment of alpha-1-antitrypsin.

Atherosclerotic plaques contain a significant number of macrophage foam cells and are associated with an inflammatory state. Inflammation induces the secretion from monocytes and other cells of cytokines, reactive oxygen species, proteinases and proteinase inhibitors among many other molecular species. AAT is prominent among the serine proteinase inhibitors and is an important regulator of leukocyte elastase and proteinase-3. It has been shown that the stable AAT-proteinase complex can upregulate AAT biosynthesis, and we have shown that the shorter, carboxyl terminal peptide (C-36) resulting from proteinase cleavage of AAT polymerizes, and in its fibrillar form alters cellular metabolism. To test for a possible link between the inflammation-generated C-36 peptide and cellular processes associated with atherogenesis, we have studied the effects of the fibrillar form of this peptide at varying concentrations on human monocytes in culture. We have found that fibrillar C-36 at concentrations of greater than or equal to 5 micromol/l in monocyte cultures for 24 h significantly increases LDL binding and uptake, upregulates LDL receptors, induces cytokine production and glutathione reductase activity, and upregulates AAT synthesis. The expression of CD36 protein, LDL Scavenger receptor, is also upregulated by fibrillar C-36 and native LDL in the presence of C-36-activated monocytes is more oxidized than with unactivated control monocytes. The majority of monocytes cultured for 24 h in the presence of C-36 fibrils were transformed morphologically into macrophages. These data establish a direct molecular link, mediated by C-36 peptide of AAT, between inflammation and the oxidation and accumulation of lipid in monocyte-derived macrophages. This may be important for an understanding of the events conducive to atherogenesis.

Analysis of Variance↗
PubMed1999

Surveillance of antibiotic resistance in ICUs in southeastern Sweden. ICU Study Group of the South East of Sweden.

BACKGROUND: A study was designed to assess a computer-based program for continuous registration of antibiotic resistance, statistics concerning severity of illness, and consumption of antibacterial drugs. METHODS: The frequency of antibiotic resistance among bacteria in eight ICUs in southeastern Sweden was investigated yearly from 1995 through 1997. The antibiotic consumption in the ICUs was registered as defined daily doses (DDD) and compared to severity of illness (APACHE-II scores). RESULTS: There was a statistically significant increase in ampicillin resistance among Enterococcus spp. between 1996 and 1997, which was due to a shift from Enterococcus faecalis to Enterococcus faecium. A high prevalence of resistance among coagulase-negative staphylococci to oxacillin (approximately 70%), ciprofloxacin (approximately 50%), fucidic acid (approximately 50%) and netilmicin (approximately 30%) was seen in all ICUs during the whole study period. There was a statistically significant increase in ciprofloxacin resistance among Escherichia coli and Enterococcus spp. The resistance among Enterobacter spp. to cefotaxime decreased but this change was not statistically significant. Efforts were made to avoid betalactam antibiotics, except carbapenems, for treatment of infections caused by Enterobacter spp. and the consumption of cephalosporins decreased whereas the consumption of carbapenems increased. The total antibiotic consumption decreased by 2.5% during the study period. There was no correlation between APACHE II scores and antibiotic consumption. CONCLUSIONS: Each ICU within a hospital ought to have a program for "on-line" antibiotic resistance surveillance of drugs used in that unit so that changes in empirical treatment can be made when there is an increase in antibiotic-resistant isolates within that unit.

APACHE↗
PubMed1999

Extrahepatic manifestations of chronic hepatitis C infection and the interrelationship between primary Sjögren's syndrome and hepatitis C in Swedish patients.

OBJECTIVE: To analyse the frequency of some extrahepatic manifestations of chronic hepatitis C virus (HCV) infection in northern European patients, including a postulated association between HCV and primary Sjögren's syndrome (SS). DESIGN: Cohort study. SETTING: Department of Medicine, Malmö University Hospital, Sweden. PATIENTS: Twenty-one patients with HCV infection and 53 with primary SS (according to the Copenhagen criteria). MAIN OUTCOME MEASURES: Cryoglobulins were analysed in all patients, while patients with primary SS were investigated with regard to markers of HCV infection, and HCV patients with objective tests of SS (Schirmer-1 test, break-up time, van Bijsterveld score, sialometry, labial salivary gland biopsy) and antibodies against nuclear antigens, smooth muscle (SMA) and mitochondria (AMA). HCV antigens in small salivary glands from lower lip biopsies were detected by immunohistochemical analysis. RESULTS: Only one of the SS patients had detectable cryoprecipitates, while another was HCV-positive. None of the 21 HCV patients had cryoprecipitates. A total of 14/21 (67%) patients with HCV infection had at least one abnormal objective test suggestive of xerostomia or keratoconjunctivitis sicca, while eight (38%) had objective evidence of both eye and salivary gland involvement. HCV antigens were not detected in affected glands. Only two patients had clinical symptoms of SS, and two fulfilled the Copenhagen criteria for SS. None of the HCV-positive patients had detectable antibodies against SS-A, SS-B, RNP, Jo-1, PCNA or Scl-70, and the frequency of ANA/SMA/AMA was low. CONCLUSIONS: While involvement of salivary and lacrimal glands was common in Swedish patients with HCV infection, cryoglobulinaemia was not observed. The pathogenetic mechanism responsible for glandular inflammation appears to be different from that in primary SS. HCV infection does not seem to be an aetiological factor for primary SS in this population. These observations suggest that viral, genetic or possibly environmental factors may be responsible for the reported high frequencies of systemic complications associated with chronic hepatitis C infection in southern Europe.

Adult↗
PubMed1999

Evidence of gastrointestinal immune reactivity in patients with sarcoidosis.

OBJECTIVES: The aim of the present study was to explore the frequency of clinical and serological manifestations of gastrointestinal immune reactivity in a large group of Swedish patients with sarcoidosis. DESIGN: In patients with documented sarcoidosis, the presence of pernicious anaemia and coeliac disease was examined. Antibodies to H+/K+ ATPase, gliadin (AGA-IgA/IgG) and endomysium (IgA-EMA) were analysed. In H+/K+ ATPase antibody-positive patients, serum gastrin levels were measured and, when elevated, gastrointestinal biopsy was offered (biopsy performed in 6/9 patients): biopsy was also offered to those with positive EMA or AGA of either class (biopsy performed in 8/12 patients). Subjects from national and local studies were used as controls. SETTING: The patients were recruited at the Department of Pulmonary Medicine, and the study was conducted at the Department of Endocrinology, University of Lund, Malmö University Hospital, Malmö, Sweden. SUBJECTS: Of all patients (n = 89) with documented sarcoidosis attending the Department of Pulmonary Medicine between January 1980 and December 1991, 78 [34 females and 44 males; median age at the time of the study, 48 (range 22-81) years; median observation time since the diagnosis of sarcoidosis, 120 (range 1-468) months] were examined. RESULTS: Twenty-nine patients (37.2%) had signs of gastrointestinal immune reactivity. H+/K+ ATPase antibodies were detected in 19 patients (24.4 vs. 4% in controls, P = 0.00015). Serum gastrin levels (median 45, range 22-720 pmol L(-1)) in those patients correlated with antibody titre (r2 = 0.882). Gliadin antibodies were detected in 12 patients (15.4 vs. 8.1% in controls, P = 0.042), of whom 11 (14.1 vs. 4.5% in controls, P = 0.00114) had AGA-IgA alone. One patient had pernicious anaemia and another coeliac disease (EMA-positive). CONCLUSION: We have demonstrated a high frequency of gastric autoimmunity and gluten-associated immune reactivity in patients with sarcoidosis, occurring in almost 40% of the cases, the former being the most frequent gastrointestinal immune manifestation. Despite a high frequency of humoral autoimmunity, the frequencies of clinical disease, pernicious anaemia and coeliac disease were not increased as compared with the control population.

Adult↗
PubMed1999

Autoaggregation of Lactobacillus reuteri is mediated by a putative DEAD-box helicase.

We have cloned and sequenced a gene from Lactobacillus reuteri that encodes a 56 kDa protein, which mediates autoaggregation of the bacteria. Using an antiserum raised against extracellular proteins from the pig intestinal isolate L. reuteri 1063, we screened a genomic lambda library derived from the same strain. Affinity purification of recombinant protein from the isolated lambda clones showed that one type of clone expressed a protein that efficiently aggregated the parental strain when added to the bacteria. Subcloning and introduction of the corresponding gene, here denoted aggHinto the L. reuteri type strain markedly enhanced aggregation. Furthermore, insertional inactivation of aggH in strain 1063 resulted in an autoaggregation-deficient phenotype. Finally, an affinity-purified and cleaved fusion of AggH protein and the maltose-binding protein, MBP, strongly promoted aggregation of L. reuteri 1063, whereas the uncleaved fusion protein was inactive. Sequencing of aggH revealed that the corresponding protein has extensive sequence homology to the large family of ATP-dependent DEAD-box helicases. These results are intriguing in view of earlier data on the promotion of genetic exchange in Lactobacillus by aggregation.

Amino Acid Sequence↗
PubMed1999

Human monocyte activation by cleaved form of alpha-1-antitrypsin involvement of the phagocytic pathway.

Production of alpha-1-antitrypsin (AAT) by human monocytes is an important factor in controlling tissue damage by proteases in the microenvironment of inflammation. Increases, of four- to eightfold, in numbers of macrophages and levels of AAT and its cleavage fragments have been found in various inflammatory loci. We have found that the C-terminal peptide (C-36) of AAT, produced by specific proteinase cleavage when added in its fibrillar form at concentrations >/=5 microM to monocytes in culture for 24 h, significantly increases low density lipoprotein (LDL) binding and uptake, up-regulates levels of LDL receptors and also induces proinflammatory cytokine (interleukin-1, interleukin-6 and tumour necrosis factor alpha) production and glutathione reductase activity. Because it is known that various cells selectively internalize surface receptors and their ligands through receptor-mediated endocytosis via clathrin-coated pits, we tested whether antibodies raised against the clathrin heavy chain would block the effects of the fibrillar form of C-36 on human monocytes in culture. Addition of excess anti-(clathrin HC) with 10 microM fibrillar C-36 diminished the stimulatory effects of the latter on LDL binding, uptake and LDL receptor levels. In contrast, however, in the presence of anti-(clathrin HC), the potentially cytotoxic effects of fibrils, such as induction of cytokines, free radicals and cytosolic activity of cathepsin D, were much greater than those observed when cells were treated with fibrils alone. These results suggest that endocytosis is the pathway by which C-36 fibrils upregulate LDL receptors, and may be the natural mechanism for fibril clearance. We infer that human monocytes clear C-36 fibrils by a clathrin-dependent pathway, presumably endocytotic, and that loss of this pathway amplifies the cytotoxic effects of the fibrils by increasing their availability to other specific or nonspecific sites through which they exert their cytotoxic effects.

Base Sequence↗
PubMed1999

Fibrillar Alzheimer's amyloid peptide Abeta(1-42) stimulates low density lipoprotein binding and cell association, free radical production and cell cytotoxicity in PC12 cells.

Amyloid forming peptides are known to disturb vital cellular functions and induce cell death. However, the mechanisms by which fibrillogenic peptides induce cytotoxic effects in various cells has not been established. In this study the effects on low density lipoprotein binding and uptake of fibrils of the Alzheimer's amyloid beta-peptide (Abeta(1-42)), which is known to play a central role in the pathogenesis of Alzheimer's disease, were investigated in pheochromocytoma PC12 cells. Fibrillar Abeta(1-42) at micromol concentrations increased low-density lipoprotein (LDL) binding and cell association by 460% and 200% respectively, and LDL degradation by about 62%. Approximately 49% and 34% of Abeta fibril stimulated LDL cell association and degradation was inhibited by anti-LDL receptor antibodies. The soluble form of Abeta had no effect on any of these measures of LDL metabolism. The observed increased glutathione reductase activity, DNA fragmentation (TUNEL assay) and decreased DNA synthesis ([(3)H] thymidine incorporation assay) in cells treated with Abeta(1-42) fibrils alone or together with LDL relative to controls, suggests that the interaction of fibrils with LDL receptors might be one possible pathway which contributes to fibril cytotoxicity.

Alzheimer Disease↗
PubMed1999

The prevalence and clinical significance of alpha 1-antitrypsin deficiency (PiZ) and ANCA specificities (proteinase 3, BPI) in patients with ulcerative colitis.

Our aim was to determine the prevalence of the PiZ allele for alpha 1-antitrypsin (AAT) deficiency and some relevant antineutrophil cytoplasmic antibody (ANCA) specificities in patients with ulcerative colitis (UC), and explore a possible association between these markers. In addition, we studied the relation to disease extension and activity. Sera from 141 patients with UC (72 women) were analyzed while 50 blood donors and 54 patients with acute myocardial infarction served as controls. Serum samples were screened for PiZ with ELISA and phenotyped by isoelectric focusing. BPI-ANCA and PR3-ANCA were detected by ELISA. Results were that 8.5% (12/141) of the patients with UC were PiZ carriers, higher than expected in the general Swedish population (4.7%) (p = 0.03). There was a significant difference between PiZ-carriers and non-PiZ-carriers in the extension and severity of colitis (odds ratio = 4.1, confidence interval = 1.1, 14.9; p = 0.028, and odds ratio = 9.0, confidence interval = 1.1, 73.3; p = 0.015; respectively). BPI-ANCA and PR3-ANCA were detected in 20.5% (29/141) and 12% (17/141) (p < 0.05 compared with controls for all parameters). Occurrence of BPI-ANCA and PR3-ANCA was not related to extension or severity of colitis (p > 0.05 for both variables). We observed no association between PiZ-carrier status and occurrence of BPI-ANCA or PR3-ANCA. The increased frequency of heterozygosity for the PiZ variant of AAT deficiency among patients with UC might imply a role played by protease inhibitors for regulation of inflammation and immunologic response in UC.

Adolescent↗
PubMed1999

The trophoblastic epithelial barrier is not infected in full-term placentae of human immunodeficiency virus-seropositive mothers undergoing antiretroviral therapy.

To study the mechanism of the placental barrier function, we examined 10 matched samples of term placentae, cord blood, and maternal blood obtained at delivery from human immunodeficiency virus (HIV)-infected mothers with children diagnosed as HIV negative in Sweden. All placentae were histologically normal, and immunochemistry for HIV type 1 p24 and gp120 antigens was negative. Highly purified trophoblasts (93 to 99% purity) were negative for HIV DNA and RNA, indicating that the trophoblasts were uninfected. Although HIV DNA was detected in placenta-derived T lymphocytes and monocytes, microsatellite analysis showed that these cells were a mixture of maternal and fetal cells. Our study indicates that the placental barrier, i.e., the trophoblastic layer, is not HIV infected and, consequently, HIV infection of the fetus is likely to occur through other routes, such as breaks in the placental barrier.

Anti-HIV Agents↗
PubMed1998

The C-terminal peptide of alpha-1-antitrypsin increases low density lipoprotein binding in HepG2 cells.

Hydrophobic fragments generated from various proteolytically degraded precursor proteins are known to form amyloid fibrils which have biological effects unrelated to precursor function. We examined the effects on HepG2 cells of the fibrillar and soluble C-terminal peptide [AAT-(358-394)] generated during the cleavage of the alpha-1-antitrypsin molecule by target proteinase. Soluble and fibrillar forms of AAT-(358-394)-peptide increased low-density lipoprotein (LDL) binding by 1-fold and 15-fold, respectively, an effect which was diminished by incubation or coincubation of cells with LDL, but was not affected by the serpin-enzyme complex. This effect of AAT-(358-394)-peptide appears to be on LDL receptor binding and not on the serpin-enzyme complex (SEC) or LDL receptor-related protein binding. The terminal deoxynucleotidyl transferase-biotin dUTP nick-end labeling assay for apoptosis showed increased DNA fragmentation in cells incubated with AAT-(358-394)-peptide fibrils relative to controls and LDL-incubated cells. [3H]Thymidine incorporation in cells incubated with fibrils for 4 days decreased by 60%. We conclude that interaction of AAT-(358-394)-peptide fibrils with cell surface receptor(s) disturbs intracellular cholesterol homeostasis and induces cell death.

Endocytosis↗