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M Thelen

Publications and source records attributed to M Thelen.

At least 55 records · Page 3Linked to original sources

Low-field MR arthrography of the shoulder joint: technique, indications, and clinical results.

In the age of cost containment and urgent reductions in health care expenditures, new options have to be explored to satisfy both diagnostic requirements and economic limitations. The introduction of low-field MR systems for assessment of joint disorders seemed to be an option for lower costs. The purpose of this article is to summarize available experiences with low-field MR arthrography of the glenohumeral joint with respect to image quality and diagnostic accuracy in detecting labral and rotator cuff lesions. Up to now, there has been only a limited number of studies available dealing with low-field MR arthrography of the glenohumeral joint. They reveal that, despite a minor image quality in comparison with high-field imaging, low-field MR arthrography of the shoulder allows for sufficient evaluation of intra- and extra-articular structures in the detection of major abnormalities such as glenohumeral instability or rotator cuff disease. Furthermore, open-configured MR scanners enable kinematic studies: Besides the analysis of normal motion, pathological findings in patients with instabilities and impingement syndrome can be delineated. They further offer the possibility for performing MR imaging-guided arthrography of the shoulder. This was first described using an open C-arm scanner with a vertically oriented magnetic field so that MR arthrography may be performed in one setting.

Arthrography↗

Non-invasive magnetic resonance imaging of coronary bypass grafts. comparison of the haste- and navigator techniques with conventional coronary angiography.

OBJECTIVE: The aim was the study was to evaluate the patency of coronary artery bypass grafts with the 3D Navigator and the Haste magnetic resonance imaging techniques. MATERIAL AND METHODS: Thirty-four patients with 82 grafts (18 internal mammarian artery and 64 saphenous venous grafts) were examined at 1.5 T using a phased arrray body coil. A 2D T-2 weighted turbo spin echo sequence (Haste) and a 3D-angiography sequence in navigator technique were used. Reference method was the conventional coronary angiography that was performed within 7 days. RESULTS: With the HASTE sequence 54 of 56 patent and 12 of the 16 occluded grafts were recognized, the sensitivity and specificity was 96 and 75%. The distal anastomosis could be assessed in 28 of 76 cases. With the Haste sequence 54 of the 56 patent and 12 of the 14 occluded grafts were detected correctly. Eight patent and two occluded grafts were judged as not assessable. The sensitivity and specificity was 96 and 85%. Sixty-six percent (50/76) of the distal anastomosis were identified correctly. With both sequences none of the bypass stenosis could be detected. CONCLUSIONS: The patency of coronary bypass grafts can be evaluated noninvasively with a sensitivity of 96% and a specificity of 76%. No inference can be made with respect to the nature of bypass graft stenosis. Better results can be expected with the development of a blood pool contrast medium, an improvement of the spatial resolution and in the combination of flow measurements.

Aged↗

3He-MRI-based vs. conventional determination of lung volumes in patients after unilateral lung transplantation: a new approach to regional spirometry.

BACKGROUND: To use 3Helium (3He)-MRI in patients with unilateral lung grafts to assess the contributions of graft and native lung to total ventilated lung volume, and second to compare conventional measurements of intrapulmonary gas volume (spirometry, body plethysmography) with image-based volumetry of ventilated lung parenchyma visualized by hyperpolarized 3He-MRI. METHODS: With Ethics Committee approval, five patients with single lung transplantation (SLTX) for idiopathic pulmonary fibrosis (IPF) underwent both conventional pulmonary function testing (PFT) and 3He-MRI of the lung. Intrapulmonary gas volume (GV) during the inspiratory breathhold for 3He-MRI was calculated from measured functional residual capacity (corrected for supine position) and inspired tidal volume. Image-based global and regional lung volumetries (LV) were performed in three-dimensionally reconstructed 3He-MR images (corrected for the fraction of tissue and blood). RESULTS: Transplanted lungs were characterized by a homogeneous distribution of signal intensity, whereas the native lungs of the patients suffering from IPF displayed an inhomogeneous signal distribution pattern with numerous round or wedge-shaped ventilation defects. Total ventilated lung volume determined by 3He-MRI correlated well with PFT-based measurements, but with a systematic overestimation of the 3He-based lung volumetry of approximately 20%. Functioning lung grafts contributed 66+/-6% and their corresponding native IPF lungs 34+/-6% to total ventilated volume (P<0.05; mean+/-SD). CONCLUSION: 3Helium-MRI of the lung offers a novel approach to regional determination of ventilated lung volume, including its blood and tissue compartments. The advantage of this technique over computed tomography or ventilation scintigraphy is the lack of radiation exposure, and hence its repeatability. Follow up of SLTX patients with this new technique may allow the monitoring of functional and structural developments of grafted lungs with better sensitivity and specificity than PFT.

Female↗

[Preliminary results of coronary artery examination using a 3D-navigator sequence on a high performance MR system].

PURPOSE: To evaluate MR coronary angiography using a three-dimensional navigator echo sequence on a MR scanner with a high performance gradient system. MATERIAL AND METHODS: Five healthy volunteers were examined with a 1.5 Tesla MR system, using a high performance prototype gradient system (peak amplitude 50 mT/m, rising time 600 mus). For imaging, a navigated gradient-echo pulse sequence with an in-plane resolution between 0.63 x 0.63 and 0.78 x 0.78 mm2 was used. Per patient two overlapping slabs were acquired. The number of visualized coronary artery segments was estimated (AHA classification). In addition, signal-to-noise measurements were performed in the ascending aorta at the level of the proximal right and left coronary arteries. RESULTS: In all volunteers the left main, the right coronary artery up to segment 3, the LAD up to segment 8 and the RCX with segment 11 and 13 were clearly visualized. The average signal-to-noise value at the level of the right coronary artery was 11.4 +/- 5.0, at the level of the left coronary artery 12.3 +/- 4.5. One volunteer was measured with an in-place resolution of 0.63 x 0.63 mm2. This resulted in a too low signal-to-noise ratio so that an adequate assessment of coronary arteries was no longer possible. CONCLUSION: 3D-MR coronary angiography using the navigator technique is limited by the signal-to-noise ratio.

Adult↗

[Evaluation of myocardial perfusion reserve in patients with CAD using contrast-enhanced MRI: a comparison between semiquantitative and quantitative methods].

OBJECTIVE: Comparison between two semiquantitative methods and a quantitative evaluation of myocardial blood flow (MBF) for assessment of myocardial perfusion reserve (MPR) in patients with CAD. MATERIAL AND METHODS: 9 patients with coronary stenoses > 50 % were examined with an ECG-gated Saturation Recovery Turbo FLASH sequence by using Gd-DTPA as contrast agent (CA). The entive measurements were performed both during rest and hyperemia induced by adenosine. The up-slopes of the signal-time S(t) curves in the myocardium and left ventricular (LV) cavity were evaluated by a linear fit. MPR was calculated from the original up-slopes of the myocardial S(t) curves and from the up-slopes, which were normalized to the up-slopes of the LV S(t) curves, respectively. For quantification of MBF values, the mathematical model MMID 4 was used and MPR was evaluated from the MBF values. RESULTS: With all tested methods, MPR was reduced in myocardial regions subtended by arteries with stenoses >/= 70 % compared with remote regions. With MMID 4 and the normalized up-slope method, differences between severe ischemic and remote regions were statistically significant. CONCLUSION: The up-slope method with normalization and quantification with MMID 4 are more sensitive methods to differentiate between remote and ischemic myocardium than the up-slope method without normalization.

Adult↗

[Determination of the distribution volume of contrast media solutions injected intrahepatically: pre-pilot studies for intratumoral gene therapy].

PURPOSE: Determination of the intrahepatic distribution volume of two contrast media (CM) by CT-guided application in an ex-vivo and an in-vivo model (pig liver). MATERIAL AND METHODS: In pig livers ex-vivo and in-vivo, 131 CT-guided injections of two different CM (Imagopaque(R), Visipaque(R)) were performed using catheters and cannula with and without side-holes and documented by spiral CT. The distribution pattern was assessed visually: interstitial, subcapsular, vascular/tubular, the distribution volume was quantified using a density mask (thresholds 70/400 HE). RESULTS: Purely interstitial applications were achieved more frequently in-vivo than ex-vivo (p = 0.001). There were no relevant differences between the two CM. Catheters without side-holes led to more interstitial CM depots than catheters with side-holes (p = 0.005). The mean distribution volume was larger with catheters with side-holes (ex-vivo 103 cm(3), in-vivo 19 cm(3)) than with catheters without side-holes (ex-vivo 67 cm(3), in-vivo 13 cm(3)) (p = 0,01). At the same time, the mean density with catheters with side-holes (102 HE) was lower than with catheters without side-holes (115 HE) (p = 0.005). CONCLUSION: Marked differences of the CM distribution volumes were observed between ex-vivo and in-vivo studies in the pig model. Catheters with side-holes are far superior to catheters without.

Animals↗

[Chronic thromboembolic pulmonary hypertension: diagnostic impact of Multislice-CT and selective Pulmonary-DSA].

PURPOSE: To evaluate the diagnostic impact of multislice-CT and selective pulmonary DSA in chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: 994 vessel segments of 14 consecutive patients with CTEPH were investigated with multislice-CT (slice thickness 3 mm, collimation 2.5 mm, reconstruction intervall 2 mm) and selective pulmonary DSA (posterior-anterior, 45 degrees oblique, and lateral projection. Analysis was performed by 2 investigators independently for CT and DSA. Diagnostic criteria were occlusions and non-occlusive changes like webs and bands, irregularities of the vessel wall, diameter reduction and thromboembolic depositions at different levels from central pulmonary arteries to subsegmental arteries. Reference diagnosis was made by synopsis of CT and DSA by consensus. RESULTS: Concerning patency CT and DSA showed concordant findings overall in 88.9 %, 92.9 % for segmental arteries and 85.4 % for subsegmental arteries. Concerning any thromboembolic changes, multislice-CT was significantly inferior to selective DSA (concordance 67.0 % overall, 70.4 % for segments and 63.6 % for subsegments). Non-occlusive changes of the vessels were significantly underdiagnosed by CT (concordance of CT versus DSA: 23.1 %). CONCLUSION: Multislice-CT and selective pulmonary DSA are equivalent for diagnosis of vessel occlusions at the level of segmental and subsegmental arteries. However, for visualisation of the non-occlusive thromboembolic changes of the vessel wall selective pulmonary DSA is still superior compared to multislice-CT. Multislice-CT and selective pulmonary DSA are complementary tools for diagnosis and treatment planning of chronic thromboembolic pulmonary hypertension (CTEPH).

Angiography, Digital Subtraction↗

[Endovascular aneurysm treatment: Radiological and macropathological findings of the endoluminal surface of modular stent grafts].

PURPOSE: Characterization of the endoluminal surface of a modular stent graft and correlation of macropathological findings with results of radiological methods. METHODS: Aneurysms of the infrarenal aorta were created in 36 mongrel FBI dogs using autologous material. Endovascular treatment was performed with modular stent grafts using two polyester-covered nitinol stents connected with overlap within the aneurysm. Follow-up was 1 and 6 weeks, and 6 months for 12 animals, respectively. Results were documented using sonography, intravascular ultrasound (IVUS), spiral CT, MRI, and digital subtraction angiography (DSA). After fixation, the aorta was prepared and incised lengthwise. Before histopathological work-up, the different segments were macropathologically characterized and correlated with the respective findings of the radiological methods. RESULTS: 4 cases showed high grade stenosis within the stent grafts and graft occlusion occurred in two cases. The connection sites of these modular stent grafts showed steps and partial separation of the graft components was causative in 5 of these cases. Migration of graft components occurred in three cases, one of them with complete disconnection of the modular device. Irregulartities and deposits on the endoluminal surface were systematically underestimated with all radiological techniques used. IVUS showed moderate concordance concerning deployment and unfolding of the stent graft, however, irregularities of the endoluminal surface were systematically underestimated. Concordance of MRI, sonography, and CT was worse. Contrast-enhanced T1-w MRI detected endoluminal deposits with moderate concordance. However, the thickness of deposits was underestimated. DSA, IVUS, and CT showed only poor concordance with macropathological findings. CONCLUSIONS: The connection site of modular stent grafts predisposes to stenosis, occlusion, and disconnection of the modular device. Stent deployment and unfolding of the membrane might be examined with IVUS. MRI is useful for detecting endoluminal deposits and stenosis. However, radiological methods will underrate irregularities and deposits of the endoluminal surface.

Animals↗

[Emergency endovascular treatment of acute aortic diseases].

PURPOSE: To investigate the safety and efficacy of emergency treatment of acute aortic diseases with endovascular stent grafts. METHODS: In 11 patients (median age 55 years, range 18 - 85) with acute complications of descending aortic diseases endovascular emergency treatment was performed: traumatic aortic rupture (n = 4), penetrating ulcer with aortobronchial fistula or hematothorax (n = 4), acute type B dissection (n = 2, one with penetration, one with subacute mesenteric ischemia), and symptomatic aneurysm of the thoracic aorta (n = 1) with pain and diameter progression. 15 stent grafts were implanted (Talent n = 11, Vanguard/Stentor n = 4). Stent extension was necessary in 4 cases. In 2 cases graft extension was done during the first procedure (due to distal migration and due to the total length of the aortic aneurysm). In 2 cases graft extension was performed 5 days (due to a new aortic ulcer at the proximal stent struts) and 5 months after the initial procedure (recurrent aortobronchial fistula due to aneurysm progression). 14 of 15 implantations required general anesthesia, one symptomatic thoracic aneurysm was performed in local anesthesia and sedation. RESULTS: 14 of 15 graft procedures were performed using the femoral or iliac approach. One procedure required aortofemoral bypass grafting due to extensive arteriosclerotic stenosis and the stent graft was inserted via the bypass graft. The orifice of the subclavian artery was crossed with bare stent struts in 4 cases without neurological complications. Median follow-up is 27 months (range 6 to 72 months). In traumatic aortic ruptures, immediate sealing of bleeding was achieved and follow-up is inconspicuous at a maximum of 72 months. In cases of aortobronchial fistulas, follow-up is satisfactory (maximum 72 months) despite the necessity for reintervention and graft extension. In one acute type B dissection retrograde dissection of the aortic arch occurred during stent release with stable disease during follow-up without neurological complications. In one type B dissection with mesenteric ischemia the mesenteric blood flow was restored. A second look operation confirmed pulsatile flow in the mesenteric trunk but a total necrosis of the small intestine and the patient consequently died. CONCLUSION: Endovascular treatment is safe and effective for emergency treatment of life-threatening complications in selected acute aortic syndromes. Mid-term results are encouraging, however, regular follow-up is mandatory to recognize late complications of the stent graft.

Acute Disease↗

[The current value of percutaneous transhepatic biliary drainage].

Percutaneous transhepatic biliary drainage (PTBD) is a well established method in the treatment of obstructive jaundice. Major indications are malignant diseases. PTBD may be necessary preoperatively in cases with severe jaundice or cholangitis or as part of palliative treatment concepts. In the past, it has been proposed that a period of preoperative PTBD may improve the morbidity rates of surgery. Various studies could not prove this theory. The significance of preoperative PTBD has changed, as observed during a 15 years period in our own institution, the indications for preoperative PTBD have decreased by half. At present, the majority of treatments with PTBD are palliative (almost 70 % of all procedures). The diagnostic opportunities of the transhepatic approach (intraductal sonography, cholangioscopy, biopsy) are exploited only in few selected cases. Since the radiological approach ist considered to be invasive and related to serious complications most patients are being referred to endoscopic drainage first. Radiologists are consulted in complicated cases of jaundice and when endoscopic approaches have failed. The retrospective evaluation of more than 1000 procedures over a period of 16 years demonstrates good results with a low rate of serious complications. During the two observed periods of nine and seven years, respectively, there occurred complications like sepsis in 1.9 %/0.5 %, peritonitis in 0.5 %/0.7 %, severe bleeding in 0.5 %/1.5 %, procedure-related death in 0.8 %/0.7 %. The overall rate of serious complications was 5 %/3.4 %. These results are comparable to those of the endoscopic approach with a complication rate of 3.6-14 % and a mortality rate of 0.5 %.

Cholangiography↗

[Combination of low and high resolution T1-weighted sequences for improved evaluation of morphologic criteria in dynamic contrast enhanced MRI of the breast].

PURPOSE: Presentation of a new protocol for simultaneous acquisition of both low and high resolution T 1 -weighted images of breast lesions for dynamic contrast-enhanced MR mammography. Demonstration of possible diagnostic improvement with representative measurements in patients with suspected breast cancer by adding morphologic parameters from high resolution sequences to the analysis of the signal-time curve. MATERIALS AND METHODS: Dynamic MR imaging was performed with a 1.5 T system (Magnetom SONATA, Siemens Medical Systems, Germany) and the manufacturer's double-breast coil. Coronal T 1 -weighted 3D FLASH sequences (spatial resolution 1.25 x 1.25 mm 2; slice thickness 1.7 mm) were acquired once before and five times after administration of contrast medium (Gd-DTPA, 0.15 mmol/kg) injection. In addition, a high resolution T 1 -weighted 3D-FLASH sequence (spatial resolution, 0.63 x 0.63 mm 2) was obtained before administration of contrast medium and after the third post-contrast low-resolution sequence. Except for the acquisition matrix, all imaging parameters were identical for both 3D pulse sequences. To assure comparison of the measured signal intensities for both T 1 -weighted sequences, calibrating phantom measurements were performed using a dilution series of Gd-DTPA. RESULTS: Phantom measurements demonstrated similar signal intensities and enhancement pattern for both sequences. A combined protocol consisting of both pulse sequences can be employed and does not interfere with the signal-time curve analysis. By measuring one high resolution sequence 3:18 minutes after administration of contrast medium, morphologic features can be evaluated without interference from barely enhancing surrounding tissue. The overall study time is not increased. The improved spatial resolution slightly increases the severity of motion artifacts. CONCLUSION: The new protocol is a clever way to improve the measurement of morphologic features without relevant loss of dynamic information. It is superior to converting the entire investigation to high resolution sequences and does not add any costs by not extending or duplicating the investigation. How much the new protocol can improve the specificity or sensitivity of MR-mammography is currently investigated on a larger patient group.

Breast↗

[Cardiac MRI in suspected myocarditis].

PURPOSE: To evaluate the potential of ECG-gated breath-hold MRI in diagnosing acute myocarditis. MATERIAL AND METHODS: Cardiac MRI was performed on 21 consecutive patients with suspected myocarditis. ECG-gated breath-hold T2-weighted images with fat suppression were acquired in 3 standard views. T1-weighted imaging (FLASH) was performed 10 min after IV administration of Gd-DTPA. Laboratory data included creatine kinase, troponin T and serological tests, ECG findings and echocardiography. Imaging findings were retrospectively compared to the discharge diagnoses. Signal alterations were semiquantitatively classified. RESULTS: Acute myocarditis was diagnosed in 9 patients and cardiac sarcoidosis in 2 patients. Late enhancement was observed in 4 patients with acute myocarditis and in both patients with cardiac sarcoidosis. Semiquantitative evaluation revealed 9 true positive, 9 true negative, 1 false positive and 2 false negative results. CONCLUSION: Cardiac MRI has the potential to detect acute myocarditis and to diagnose cardiac sarcoidosis. Late enhancement of Gd-DTPA can be found in both viral myocarditis and cardiac sarcoidosis.

Acute Disease↗

Phosphatidylinositol 3-kinase c2alpha contains a nuclear localization sequence and associates with nuclear speckles.

Phosphoinositide 3-kinase C2alpha (PI3K-C2alpha) belongs to the class II phosphatidylinositol 3-kinases, which are defined by their in vitro usage of phosphatidylinositol and phosphatidylinositol 4-phosphate as substrates. All type II phosphatidylinositol 3-kinases contain at their C terminus a C2-like domain. Here we demonstrate that Homo sapiens phosphoinositide 3-kinase C2alpha (HsPI3K-C2alpha) has dual cellular localization present in the cytoplasm and in the nucleus. A distinct nuclear localization signal sequence was identified by expressing HsPI3K-C2alpha-green fluorescent protein fusion proteins in HeLa cells. The nuclear localization signal was mapped to a stretch of 11 amino acids (KRKTKISRKTR) located within C2-like domain of the kinase. In the cytoplasm and the nucleus HsPI3K-C2alpha associates with macromolecular complexes that are resistant to detergent extraction. Indirect immunofluorescence reveals that in the nucleus HsPI3K-C2alpha is enriched at distinct subnuclear domains known as nuclear speckles, which contain pre-mRNA processing factors and are functionally connected to RNA metabolism. Phosphorylation of HsPI3K-C2alpha is induced by inhibition of RNA polymerase II-dependent transcription and coincides with enlargement and rounding up of the nuclear speckles. The results suggest that phosphorylation of HsPI3K-C2alpha is inversely linked to mRNA transcription and supports the importance of phosphoinositides for nuclear activity.

Amino Acid Sequence↗

Is dimerization of chemokine receptors functionally relevant?

Chemokines activate lymphocytes by initiating signaling cascades through cell surface receptors that couple to heterotrimeric GTP-binding proteins. Thelen and Bagglioni describe why the recent proposal that these receptors form heterodimers and activate the Jak kinases for transducing signals should be viewed with caution.

Animals↗

Carboxyl-terminal modulator protein (CTMP), a negative regulator of PKB/Akt and v-Akt at the plasma membrane.

The PKB (protein kinase B, also called Akt) family of protein kinases plays a key role in insulin signaling, cellular survival, and transformation. PKB is activated by phosphorylation on residues threonine 308, by the protein kinase PDK1, and Serine 473, by a putative serine 473 kinase. Several protein binding partners for PKB have been identified. Here, we describe a protein partner for PKBalpha termed CTMP, or carboxyl-terminal modulator protein, that binds specifically to the carboxyl-terminal regulatory domain of PKBalpha at the plasma membrane. Binding of CTMP reduces the activity of PKBalpha by inhibiting phosphorylation on serine 473 and threonine 308. Moreover, CTMP expression reverts the phenotype of v-Akt-transformed cells examined under a number of criteria including cell morphology, growth rate, and in vivo tumorigenesis. These findings identify CTMP as a negative regulatory component of the pathway controlling PKB activity.

Adaptor Proteins, Signal Transducing↗

Rac and phosphatidylinositol 3-kinase regulate the protein kinase B in Fc epsilon RI signaling in RBL 2H3 mast cells.

FcepsilonRI signaling in rat basophilic leukemia cells depends on phosphatidylinositol 3-kinase (PI3-kinase) and the small GTPase Rac. Here, we studied the functional relationship among PI3-kinase, its effector protein kinase B (PKB), and Rac using inhibitors of PI3-kinase and toxins inhibiting Rac. Wortmannin, an inhibitor of PI3-kinase, blocked FcepsilonRI-mediated tyrosine phosphorylation of phospholipase Cgamma, inositol phosphate formation, calcium mobilization, and secretion of hexosaminidase. Similarly, Clostridium difficile toxin B, which inactivates all Rho GTPases including Rho, Rac and Cdc42, and Clostridium sordellii lethal toxin, which inhibits Rac (possibly Cdc42) but not Rho, blocked these responses. Stimulation of the FcepsilonRI receptor induced a rapid increase in the GTP-bound form of Rac. Whereas toxin B inhibited the Rac activation, PI3-kinase inhibitors (wortmannin and LY294002) had no effect on activation of Rac. In line with this, wortmannin had no effect on tyrosine phosphorylation of the guanine nucleotide exchange factor Vav. Wortmannin, toxin B, and lethal toxin inhibited phosphorylation of PKB on Ser(473). Similarly, translocation of the pleckstrin homology domain of PKB tagged with the green fluorescent protein to the membrane, which was induced by activation of the FcepsilonRI receptor, was blocked by inhibitors of PI3-kinase and Rac inactivation. Our results indicate that in rat basophilic leukemia cells Rac and PI3-kinase regulate PKB and suggest that Rac is functionally located upstream and/or parallel of PI3-kinase/PKB in FcepsilonRI signaling.

Animals↗

Rapid inactivation of stromal cell-derived factor-1 by cathepsin G associated with lymphocytes.

The CXC chemokine stromal cell-derived factor (SDF)-1 is produced constitutively in different tissues. It is the only known ligand for CXCR4, which is widely expressed in leukocytes and in some tissue cells, and acts as coreceptor for X4 HIV strains. Because of the general interest in the mechanisms that regulate the activity of constitutively expressed chemokines, we have studied the inactivation of SDF-1 in cells that bear CXCR4. Here we show that B lymphocytes, NK cells and, to a lesser extent, T lymphocytes inactivate SDF-1 by N-terminal processing. Inactivation is due to cathepsin G which is associated with the membrane of lymphocytes and rapidly cleaves off five N-terminal residues by acting on the Leu(5)-Ser(6) bond yielding SDF-1(6-67). Processing was observed with intact cells, cell membrane preparations and soluble cathepsin G obtained by extraction of the membranes with Triton X-100. Cathepsin G is released by neutrophils and monocytes and binds on the surface of lymphocytes by an apparently saturable process. Analysis of the product obtained, the time course and the sensitivity to inhibitors shows that cathepsin G is the only protease involved. Conversion of SDF-1 to SDF-1(6-67) was complete within minutes to 1-2 h depending on the enzyme source, and was abrogated by inhibitors of serine proteases and chymostatin. Diprotin A, an inhibitor of dipeptidyl peptidase IV, was without effect. Owing to its availability on the surface of SDF-1-responsive cells and its rapid effect, cathepsin G is likely to play a significant role in down-regulating SDF-1 activity.

Amino Acid Sequence↗