Adhesion molecules in renal diseases

Different adhesion molecules are implicated in the pathogenesis in glomerulonephritis. Leukocyte adhesion molecules play a critical role in causing renal damage in a variety of glomerulonephritic conditions. In order to understand the mechanisms by which distinct adhesion molecules are involved in human glomerulonephritis, it is necessary to have an overview of their function in maintenance of tissue architecture, morphogenesis, immunosurveillance, inflammation, tumor growth, etc. Thus, this review addresses the role of cadherins, selectins, integrins, and members of the immunoglobulin supergene family in developing, normal, and diseased kidney with special attention to glomerulonephritis and possible new therapeutic approaches.     

Adhesion molecules in kidney diseases (part II)

Different adhesion molecules are involved in the maintenance of tissue architecture, morphogenesis, immunosurveillance, inflammation, tumour growth, etc. Thus, this review will be directed to the role of cadherins, selectins, integrins and members of the immunoglobuline supergene family in the pathogenesis of glomerulonephritis, acute renal failure, reaction of renal rejection, development of renal tumours, their invasion and metastases. A better understanding of the role of adhesion molecules in nephropathology may provide new aspects of treatment of different forms of renal diseases including tumours.     

Adhesion molecules in kidney diseases (part I)

Adhesive molecules are (glyco)proteins of the cellular membranes. All of them have their extramembranous, transmembranous and intracytoplasmatic parts. As receptor molecules, their extracellular parts bind the specific ligand. The ligand can be found on the surface of the other cell or in the extracellular matrix (basal membranes). The following families of adhesion molecules are: cadherins, selectins, integrins and members of immunoglobuline supergene family. Different members of the same family could have different times (in ontogenesis, in adult form) and space distribution (in different tissues, different tissue structures). The contact between the cells and basal membranes with these molecules is important for cell division, maintaining the tissue architecture, polarization and function of cells, migration of cells, endo- and exo-cytosis as well as for maintaining the structure and function of basal membranes. As above stated all this is important in the occurrence morphogenesis, haemostasis, inflammation, malignant cell transformation and metastasis. This knowledge is important for the better understanding of renal diseases.     

Adhesion molecules in urologic tumors

Adhesion molecules play an important role in organogenesis, would healing, inflammation, and progression of malignant tumors. Three major classes of adhesion molecules may be discriminated by function: (a) calcium-dependent homotypic adhesion molecules (e.g. cadherins), (b) substrate adhesion molecules (e.g. integrins) and (c) heterotypic adhesion molecules (e.g. ICAM-1). Molecules of each of the three classes have been identified in urologic tumors. Results of research on substrate adhesion molecules and heterotypic adhesion molecules have not yet led to new clinical concepts. In contrast, loss of E-cadherin in tumors of the bladder and prostate has been clearly associated with de-differentiation of tumors and diminished survival of patients. Loss of another adhesion molecule, C-CAM, has been observed in prostate cancer. This has led to new therapeutic approaches, which are in an experimental stage at present. It may be expected that, in the future, new therapeutic concepts will be based on research on adhesion molecules in urologic tumors.     

Adhesion molecules in clinical medicine

Cellular adhesion molecules (CAMs) are critical components in the processes of embryogenesis, tissue repair and organization, lymphocyte function, lymphocyte homing and tumor metastasis, as well as being central to the interactions between hemopoietic progenitors and bone marrow microenvironment, and between leukocytes and platelets with vascular endothelium. Expression of CAMs regulates normal hemopoiesis and migration and function of mature hemopoietic cells. CAMs are an important part of the inflammatory response and may regulate cytokine synthesis. In addition, CAM expression may be critical for tumorigenesis. Monoclonal antibodies to CAMs have been developed for clinical use; initial results suggest that these agents have great potential in the prevention and treatment of inflammation, thrombosis, reperfusion injury, and graft rejection.     

Adhesion molecules in the nickel allergic reaction

Nickel is the major cause of allergic contact dermatitis, and to increase our understanding of this immune reaction we studied changes in the expression of adhesion molecules on mononuclear cells during nickel stimulation in vivo and in vitro. Nickel-induced lymphocyte cultures were used in vitro, the cells being examined with monoclonal antibodies (Mabs) and by flow cytometry. Mononuclear cells from skin biopsies of in vivo cutaneous nickel reactions were studied with Mabs and immunohistochemistry. The expression of adhesion molecules in vitro was differential: the number of cells carrying CD11c, CD29, CDw49b, CDw49d, CDw49e, CDw49f, CD54, CD56 and ELAM-1 being significantly overrepresented among the nickel-induced lymphoblasts whereas the number of blasts carrying CD44 was underrepresented and those of CD11a, CD18, CD58 and LAM-1 remained unchanged. CD4+ cells gained adhesion molecules during nickel-induced blast transformation whereas CD8+ cells lost most of their adhesion molecules. The in vivo results were in agreement with the in vitro ones except that CDw49b, CDw49f, CD56 and ELAM-1 could not be detected in a 96-hour nickel reaction in vivo. In conclusion, the nickel allergic reaction favors the expression of certain adhesion molecules, and this expression is induced on CD4+ cells while CD8+ cells tend to lose such molecules. The changes were more sensitively detected with the in vitro method.     

Adhesion molecules during immune response to exercise

PURPOSE: The extracellular matrix serves as a structural support for the corneal stroma and mediates signaling events that regulate the intracellular environment of stromal keratocytes. We hypothesize that adhesion and injury mediate signal transduction events causing the phosphorylation of tyrosine residues of specific adhesion proteins and that phosphorylation is required for cellular adhesion and migration. METHODS: For the adhesion experiments; primary rabbit stromal fibroblasts were seeded and phosphorylation of tyrosine residues was followed from 1 min to 24 h. For the injury experiments, confluent primary cultures were rendered quiescent, wounded, and tyrosine phosphorylation was followed from 30 s to 6 h. The antibody (py-20) was used to detect proteins phosphorylated on tyrosine residues. We examined changes in the phosphorylation of focal adhesion kinase (FAK), paxillin and cortactin, using immunoprecipitation and Western blot analysis. RESULTS: In the adhesion experiments, the phosphorylation of a 68-kDa protein was detected after 1 min, and the phosphorylation of a 125-kDa protein was not detected until 15 min. These proteins were identified in re-probed blots as paxillin and FAK. In the injury experiments, FAK phosphorylation was detected within 30 s and remained elevated for 6 h when cells were cultured on fibronectin. Both FAK and paxillin phosphorylation were prominent after injury, but unlike FAK phosphorylation, paxillin phosphorylation decreased over time. Phosphorylation was prominent at the wound margin. After wound closure, it returned to background levels. Tyrosine kinase inhibitors, genistein and herbimycin, decreased the number of adherent cells and altered the rate of cell migration after injury, compared to control (DMSO alone). CONCLUSION: The results indicate that injury and cell-matrix interaction mediate the phosphorylation of specific adhesion proteins and that phosphorylation is required for wound repair.     

Expression of adhesion molecules and costimulatory molecules in inflammatory myopathies

To clarify the local immune responses in inflammatory myopathies, we examine recent studies on expression of adhesion and costimulatory molecules. Adhesion molecules participate in MNC influx from blood vessels into muscle tissues and interactions of inflamed muscle cells with surrounded MNC. These antigens may work as costimulatory molecules in antigen presenting process by muscle cells, as well as in augmentation of inflammation by infiltrating MNCs.     

Isotretinoin in inflammatory bowel diseases

The presenilin 1 (PS1) gene, located on chromosome 14, is the major gene involved in the autosomal dominant forms of early onset Alzheimer's disease (AD). In order to estimate the frequency of de novo PS1 mutations, we have sequenced the PS1 open reading frame in 13 clinically diagnosed patients with no affected relatives, who had developed AD before the age of 50. In one case with onset at 37 years, we identified a missense mutation resulting in a methionine to lysine substitution at codon 139 of the PS1 gene. This substitution is the fourth identified at the same codon. This study, in agreement with previous reports, suggests that de novo PS1 mutations can occur but at a low frequency.     

Chemokines and inflammatory diseases

Intoxication after ingestion of toad is rare, but it results in severe morbidity and high mortality. Recently, we encountered 2 children, one a 15-month-old boy and one a 20-month-old girl, who were fed cooked toad (Bufo melanostictus) soup. The boy expired of ventricular fibrillation. The girl presented with varying degrees of A-V block with congestive heart failure which, however, was completely resolved after intensive treatment. In our experience, early identification and intervention are necessary to decrease absorption of toxins; to correct hyperkalemia. Dysrhythmia should be treated with atropine, antiarrhythmic agents, and a temporary pacemaker, in order to avoid lethal results.     

Methotrexate use in miscellaneous inflammatory diseases

Methotrexate has proven to be a safe, effective, long-term therapy for rheumatoid arthritis. Its property as a corticosteroid-sparing drug in rheumatoid arthritis has been recognized and its potential has been explored in other inflammatory and autoimmune diseases. This article describes and analyzes the use of methotrexate for a wide variety of diseases, some of which are not the usual province of rheumatologists, to provide some guidance concerning its role for treatment. Methotrexate therapy seems promising for systemic lupus erythematosus, inflammatory myopathy, inflammatory eye disease, inflammatory bowel disease, and some manifestations of sarcoidosis. Its role in other diseases is not as well defined.     

Three-dimensional rectal ultrasonography in inflammatory bowel diseases

Authors used three-dimensional ultrasound technique in diagnosing chronic inflammatory bowel diseases to demonstrate its activity and complications. For their examinations they adopted high-(7.5 MHz) frequency rectal transducers which made it possible to depict the layers and environment of the intestinal wall. To complete endoscopy, the new method of examination is suitable to state the extent and depth of the process. In cases where they had been unable to find alterations by endoscopic examinations--though the patient had complaints--residual submucoses inflammation could be demonstrated by means of this method. This method has been employed to determine surrounding fluid, lymph node and fistula. The authors support this method by demonstrating cases. In their opinion the three-dimensional ultrasound examination is a suitable new method in the field of diagnostic, therapeutic and operational indications and follow up. The advantage of the method lies in its non-invasive and reproducible quality, its three-dimensional representation, and good resolution and its resolving power as opposed to earlier technique (fistulography) for avoiding infections.     

Adhesion molecules (E-selectin and ICAM-1) in pulmonary allograft rejection

Vascular endothelial cells act as antigen-presenting cells in the lung allograft and stimulate alloreactive host lymphocytes. Activated lymphocytes and cytokines can induce expression of leukocyte-endothelial adhesion molecules that facilitate invasion of the allograft by circulating leukocytes. To define the role of endothelial HLA class II antigen and adhesion molecule expression in lung allograft rejection, we prospectively analyzed endothelial expression of HLA class II, E-selectin, and intercellular adhesion molecule-1 (ICAM-1) antigens in 52 transbronchial biopsy specimens from 24 lung allograft recipients as compared to normal control subjects. Thirty-one of 52 specimens showed histologic rejection and 8 of 24 patients developed histologic obliterative bronchiolitis (OB) by the end of the study period. Increased expression of HLA class II antigen was seen in 32 of 52 (62%) lung allograft specimens, but increased expression did not correlate with acute rejection or OB. In contrast, E-selectin expression was seen in 30 of 52 (58%) biopsy specimens and was associated with acute rejection (p < 0.005) and with the development of OB (p < 0.05). Increased expression of ICAM-1 was seen in only 18 of 52 (35%) biopsy specimens and did not correlate with acute rejection or OB. These data suggest that E-selectin expression may be a tissue marker of acute and chronic lung rejection possibly by promoting leukocyte adhesion to the allograft endothelium. The high levels of endothelial HLA class II expression may reflect long-term antigenic stimulation of the allograft even in the absence of rejection.