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PubMed2003

Immunophenotyping of macrophages in human pulmonary tuberculosis and sarcoidosis.

Classic studies of tuberculosis (TB) revealed morphologic evidence of considerable heterogeneity of macrophages (MØs), but the functional significance of this heterogeneity remains unknown. We have used newly available specific antibodies for selected membrane and secretory molecules to examine the phenotype of MØs in situ in a range of South African patients with TB, compared with sarcoidosis. Patients were human immunodeficiency virus-negative adults and children, and the examined biopsy specimens included lung and lymph nodes. Mature pulmonary MØs (alveolar, interstitial, epithelioid and multinucleated giant cells) selectively expressed scavenger receptor type A and a novel carboxypeptidase-like antigen called carboxypeptidase-related vitellogenin-like MØ molecule (CPVL). CPVL did not display enhanced expression in sarcoidosis, vs. TB patients, as observed with angiotensin-converting enzyme (ACE), a related molecule. Immunocytochemical studies with surfactant proteins (SP)-A and -D showed that type II alveolar cells expressed these collectins, as did MØs, possibly after binding of secreted proteins. Studies with an antibody specific for the C-terminus of fractalkine, a tethered CX3C chemokine, confirmed synthesis of this molecule by bronchiolar epithelial cells and occasional endothelial cells. These studies provide new marker antigens and extend previous studies on MØ differentiation, activation and local interactions in chronic human granulomatous inflammation in the lung.

Adult↗
PubMed1995

Transforming growth factor-alpha (TGF-alpha) in human bone marrow: demonstration of TGF-alpha in erythroblasts and eosinophilic precursor cells and of epidermal growth factor receptors in blastlike cells of myelomonocytic origin.

The expression of transforming growth factor-alpha (TGF-alpha) in human differentiating leukemic cell lines and in circulating human eosinophils prompted the search for an analogous function in normal human bone marrow (BM) cells. Immunohistochemistry, using a monoclonal antibody directed to the mature form of the TGF-alpha molecule, showed TGF-alpha on the erythroblasts of normal donors. This novel property of erythroid cells was found on cells at all stages of maturation, most clearly on nucleated forms but to some extent also on erythrocytes within the BM. The presence of membrane-bound TGF-alpha on erythroblasts was confirmed by immunomagnetic cell sorting with polyclonal TGF-alpha antibodies; the recovered cells consisted almost entirely of erythroblasts. Using another monoclonal antibody directed to TGF-alpha, immunohistochemistry showed a different pattern of positive cells including eosinophilic precursor cells, in accordance with earlier findings in blood eosinophils. In addition, the TGF-alpha immunoreactivity was shown in promyelocytes and neutrophilic myelocytes. The presence of epidermal growth factor (EGF) receptor mRNA in BM cells was demonstrated by reverse transcription polymerase chain reaction, whereas EGF receptor-carrying cells were recognized by immunohistochemistry, using polyclonal antibodies directed to the cytoplasmic part of the EGF receptor. The EGF receptor-positive cell constituted about 3% of the nucleated BM cell population. It was classified as a blastlike cell of myelomonocytic origin by morphologic criteria and CD68 positivity. Our results may indicate a novel function of TGF-alpha in erythrocytic differentiation.

Antibodies, Monoclonal↗
PubMed2002

Cloning and characterization of human Siglec-11. A recently evolved signaling molecule that can interact with SHP-1 and SHP-2 and is expressed by tissue macrophages, including brain microglia.

Siglecs are sialic acid-recognizing animal lectins of the immunoglobulin superfamily. We have cloned and characterized a novel human molecule, Siglec-11, that belongs to the subgroup of CD33/Siglec-3-related Siglecs. As with others in this subgroup, the cytosolic domain of Siglec-11 is phosphorylated at tyrosine residue(s) upon pervanadate treatment of cells and then recruits the protein-tyrosine phosphatases SHP-1 and SHP-2. However, Siglec-11 has several novel features relative to the other CD33/Siglec-3-related Siglecs. First, it binds specifically to alpha2-8-linked sialic acids. Second, unlike other CD33/Siglec-3-related Siglecs, Siglec-11 was not found on peripheral blood leukocytes. Instead, we observed its expression on macrophages in various tissues, such as liver Kupffer cells. Third, it was also expressed on brain microglia, thus becoming the second Siglec to be found in the nervous system. Fourth, whereas the Siglec-11 gene is on human chromosome 19, it lies outside the previously described CD33/Siglec-3-related Siglec cluster on this chromosome. Fifth, analyses of genome data bases indicate that Siglec-11 has no mouse ortholog and that it is likely to be the last canonical human Siglec to be reported. Finally, although Siglec-11 shows marked sequence similarity to human Siglec-10 in its extracellular domain, the cytosolic tail appears only distantly related. Analysis of genomic regions surrounding the Siglec-11 gene suggests that it is actually a chimeric molecule that arose from relatively recent gene duplication and recombination events, involving the extracellular domain of a closely related ancestral Siglec gene (which subsequently became a pseudogene) and a transmembrane and cytosolic tail derived from another ancestral Siglec.

Amino Acid Sequence↗
PubMed1994

Leishmania donovani-infected macrophages: characterization of the parasitophorous vacuole and potential role of this organelle in antigen presentation.

Leishmania donovani amastigotes, the etiological agents of visceral leishmaniasis, are obligate intracellular parasites residing in membrane-bound compartments of macrophages called parasitophorous vacuoles (PV). The study of these organelles is of paramount importance to understanding how these parasites resist the microbicidal mechanisms of macrophages and how they escape the immune response of their hosts. Confocal microscopy of mouse bone marrow-derived macrophages infected with L. donovani amastigotes and stained for various prelysosomal/lysosomal markers and for major histocompatibility complex (MHC) molecules was used to define PV with respect to the endocytic compartments of the host cells and to address the issue of their potential role in antigen processing and presentation. Forty-eight hours after infection, many PV contained cathepsins B, D, H and L and they were all surrounded by a membrane enriched for the lysosomal glycoprotein lgp120/lamp 1 but apparently devoid of the cation-independent mannose 6-phosphate receptor, a membrane protein generally absent from the lysosomes. These data suggested that PV acquire within 48 hours the characteristics of a lysosomal compartment. However, both macrosialin and the GTP-binding protein rab7p (specific markers of the prelysosomal compartment) were found to be highly expressed in/on PV membrane. Thus, at this stage, PV appear to exhibit both lysosomal and prelysosomal features. Infected macrophages activated with IFN-gamma before or after infection showed PV strongly stained for MHC class II molecules but not for MHC class I molecules. This suggests that, if infected macrophages can act as antigen-presenting cells for class I-restricted CD8+ T lymphocytes, Leishmania antigens must exit the PV. MHC class II molecules reached the PV progressively, indicating that they were not plasma membrane-bound molecules trapped during internalization of the parasites. The redistribution of class II observed in infected cells did not alter their quantitative expression on the plasma membrane at least during the first 48 hours following the phagocytosis of the parasites. The invariant chains, which are transiently associated with class II molecules during their intracellular transport and which mask their peptide-binding sites, did not reach PV or were rapidly degraded in these sites, suggesting that PV-associated class II are able to bind peptides. This last assumption is strengthened by the fact that class II located in PV could bind conformational antibodies that preferentially recognize class II with tightly associated peptides.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2003

Productive infection of dendritic cells by simian immunodeficiency virus in macaque intestinal tissues.

Dendritic cells (DCs) are potent antigen-presenting cells that likely play multiple roles in human immunodeficiency virus-1 (HIV-1) and simian immunodeficiency virus (SIV) pathogenesis. This paper describes the effects of pathogenic SIV infection on the networks of DCs in rhesus macaque (Macaca mulatta) intestinal tissues. Intestinal tissues were obtained from macaques at different stages of disease following infection with the pathogenic SIV/DeltaB670 isolate. The patterns and levels of expression of SIV and DC-associated mRNAs were examined and quantitated directly in intestinal tissue sections. In situ hybridization was performed for SIV, DC-specific ICAM3-grabbing non-integrin (DC-SIGN), DC-specific lysosome-associated membrane glycoprotein (DC-LAMP), DC-specific C-type lectin 1 (DECTIN-1), CC chemokine receptor 6 (CCR6), CCR7, and macrophage inflammatory protein 3alpha (MIP-3alpha/CCL20) mRNAs and quantitative image analysis was performed to measure mRNA expression levels. To identify the cell types productively infected by SIV, simultaneous in situ hybridization and immunohistochemical staining were performed. The DC networks in macaque intestinal tissues were found to be extensive and although they generally remained intact during the course of SIV infection, there were alterations in the expression of markers for immature DCs. One alteration was an increase in the expression in intestinal submucosa of DC-SIGN, a molecule that binds to HIV-1/SIV and increases its infectivity. Concomitant with this increase, it was found that during AIDS, the population of productively infected cells included DCs, based on co-expression of DC-SIGN and DECTIN-1 mRNAs. These data indicate that SIV infection affects subpopulations of macaque intestinal DCs, including productive infection of DC-SIGN+ DCs, the consequences of which are likely to be ongoing viral propagation and decreased immunostimulatory function.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Inflammatory events are involved in acne lesion initiation.

The earliest subclinical acne "lesion" is a microcomedone, of which hyperproliferation of the follicular epithelium is a characteristic feature. Inflammatory cells have been observed at the periphery of these "lesions". This study investigated whether inflammatory events occur pre or post hyperproliferative changes. Cellular, vascular, and proliferative markers were examined by immunohistochemical techniques on biopsies of clinically normal follicles from uninvolved skin and early inflamed lesions from acne patients. Control follicles were obtained from non-acne subjects. Follicles from uninvolved skin exhibited no microcomedonal features. Proliferation in the epithelium was comparable to controls and was significantly lower than in inflamed lesions. Numbers of CD3+, CD4+ T cells were elevated in the perifollicular and papillary dermis although levels were not equivalent to those in papules. The number of macrophages was also greatly increased and similar to those in papules. There were no changes in blood vessel numbers or vascular intercellular adhesion molecule 1 expression but E-selectin expression was increased to levels found in papules and vascular adhesion molecule 1 levels were upregulated. Levels of the pro-inflammatory cytokine interleukin-1 were also upregulated perifollicularly. Moreover, aberrant integrin expression was demonstrated in the epidermis around these uninvolved follicles and inflamed lesions whereas the basement membrane was still intact. These results provide novel evidence for vascular endothelial cell activation and involvement of inflammatory responses in the very earliest stages of acne lesion development.

Acne Vulgaris↗
PubMed1992

Recombinant interleukin-2 and lymphokine-activated killer cell treatment of advanced bladder cancer: clinical results and immunological effects.

The purpose of this study was to evaluate the efficacy of treatment with recombinant interleukin-2 (rIL-2) and lymphokine-activated killer cells in patients with advanced bladder cancer and to study the induced changes in the distribution of leukocyte subsets in blood and tumor. Nine patients with metastatic transitional cell cancer of the bladder were treated with a continuous infusion of rIL-2 combined with lymphocytes stimulated in vitro with rIL-2. None of the patients responded to the therapy despite substantial changes observed in the immunological cells, both in tumor and blood. The rIL-2 infusion induced migration of leukocytes to the tumors, which was related to increased expression of the adhesion molecule VLA-1 on both peripheral blood mononuclear cells and the endothelial cells of small tumor vessels. Only T-cells, predominately expressing IL-2 receptors, and macrophages infiltrated the tumors. Natural killer cells remained few or absent in the tumors, even though the natural killer cells in peripheral blood were activated by the treatment. This study shows that the present technique of rIL-2 and lymphokine-activated killer cell therapy is able to induce substantial changes in the immune system of patients with metastatic bladder cancer. However, this treatment did not induce tumor regression, which may be due to the advanced stage of disease.

Adult↗
PubMed1996

Human adrenal cells express tumor necrosis factor-alpha messenger ribonucleic acid: evidence for paracrine control of adrenal function.

Tumor necrosis factor (TNF) is gaining increasing importance in clinical medicine. It plays a role in the interaction of the immune system with the hypothalamic-pituitary-adrenal axis. In the present study various morphological methods, including immunohistochemistry, electron microscopy, and in situ hybridization were applied to characterize the localization and distribution of TNF in the human adrenal gland. Double immunostaining revealed an astonishing degree of intermingling of steroid-producing cells and chromaffin cells. Macrophages could be found in all regions of the adrenal gland, but particularly in the transition zone of cortex and medulla. The steroid-producing cells of the inner zone of the cortex express major histocompatibility complex class II molecules. On the ultrastructural level, immune cells, steroid cells, and catecholamine-producing cells were found in direct contact. The combination of immunohistochemistry and in situ hybridization was optimally suited to define the exact cellular source of TNF in the human adrenal. TNF is produced in macrophages, but above all in 17 alpha-hydroxylase-positive cells (steroid-producing cells) in the zona reticularis and medulla. No signal was found in chromaffin cells. TNF may induce major histocompatibility complex class II in human adrenal gland in a paracrine or autocrine manner. It is concluded that TNF may have an important role in normal human adrenal physiology.

Adrenal Cortex↗
PubMed2003

The immunohistochemical expression of metallothionein in inflammatory bowel disease. Correlation with HLA-DR antigen expression, lymphocyte subpopulations and proliferation-associated indices.

Metallothionein (MT) expression in intestinal resection specimens from 41 patients with ulcerative colitis (UC) and 10 patients with Crohn's disease (CD ) was immunohistochemically studied by the avidin-biotin (ABC) method. In addition, the possible relationship of its expression with HLA-DR antigen expression, lymphocyte subpopulations and proliferation-associated indices was studied in order to elucidate the role of this molecule in inflammatory bowel disease (IBD). The MT immunoreactivity was recorded by staining and intensity-distribution scores. MT staining varied in and was mainly localized in the cytoplasm, although a combined nuclear/cytoplasmic reactive pattern was also seen in epithelial cells. MT expression was decreased in UC, and CD compared with normal mucosa. No difference in MT expression between UC and CD was noted. In UC, a gradually decreased expression from remission, to resolving and to active phase was observed. An inverse correlation of MT expression with HLA-DR antigen expression was detected (p = 0.018) in the cases of UC. The data suggest that a low level of MT expression in inflammatory bowel disease and particularly in active phase of UC may indicate a decreased endogenous intestinal protection and it may be implicated in the pathogenesis of the disease.

Antigens, CD↗
PubMed2006

Comparative nitric oxide production by LPS-stimulated monocyte-derived macrophages from Ovis canadensis and Ovis aries.

Bighorn sheep are more susceptible to respiratory infection by Mannheimia haemolytica than are domestic sheep. In response to bacterial challenge, macrophages produce a number of molecules that play key roles in the inflammatory response, including highly reactive nitrogen intermediates such as nitric oxide (NO). Supernatants from monocyte-derived macrophages cultured with M. haemolytica LPS were assayed for nitric oxide activity via measurement of the NO metabolite, nitrite. In response to LPS stimulation, bighorn sheep macrophages secreted significantly higher levels of NO compared to levels for non-stimulated macrophages. In contrast, levels of NO produced by domestic sheep macrophages in response to M. haemolytica LPS did not differ from levels detected in non-stimulated cell cultures. Nitrite levels detected in supernatants of LPS-stimulated bighorn macrophage cultures treated with an inducible nitric oxide synthase (INOS) inhibitor, N(G)-monomethyl-L-arginine, were similar to that observed in non-stimulated cultures indicating a role for the iNOS pathway.

Antigens, CD↗
PubMed2003

Expression of the VEGF and angiopoietin genes in endometrial atypical hyperplasia and endometrial cancer.

Angiogenesis is critical for the growth and metastasis of endometrial cancer and is therefore an important therapeutic target. Vascular endothelial growth factor-A (VEGF-A) is a key molecule in angiogenesis, but the identification of related molecules and the angiopoietins suggests a more complex picture. We investigated the presence of transcripts for VEGF-A, VEGF-B, VEGF-C, VEGF-D, Angiopoietin-1 and Angiopoietin-2 in benign endometrium, atypical complex hyperplasia (ACH) and endometrioid endometrial carcinoma using in situ hybridisation. We confirmed the presence of VEGF-A mRNA in the epithelial cells of cancers examined (13 out of 13), but not in benign endometrium or ACH. We also demonstrate, using quantitative polymerase chain reaction, that levels of VEGF-B mRNA are significantly lower in endometrial cancer than benign endometrium. We conclude that loss of VEGF-B may contribute to the development of endometrial carcinoma by modulating availability of receptors for VEGF-A.

Adult↗
PubMed2001

Localization and density of myeloid leucocytes in the periodontal ligament of normal rat molars.

The phenotypic distribution and density of macrophage-associated antigen-expressing cells in the periodontal ligament (PDL) of normal rat mandibular first molars was evaluated by immunohistochemistry, and an attempt made to identify dendritic cells (DCs) by immunoelectron microscopy. Cells immunopositive to ED1 (a general macrophage marker) were widely distributed throughout the PDL and were most common around blood vessels. A small number of T lymphocytes and OX62 (anti-veiled cells and gammadelta T cells)-positive DC-like cells were also found. The relative density of cells immunopositive to ED9 (CD14), OX42 (CD11b), OX6 (anti-class II MHC molecules), ED2 (anti-tissue-resident macrophages), 8A2 (CD11c) and WT.1 (CD11a) varied in the mesial, distal and periapical regions of the distal root and the furcal region. This finding suggests that there are several subpopulations of ED1-positive cells which express various combinations of these markers. Immunoelectron microscopy revealed that a small, but distinct, subpopulation of ED1- and OX6-positive cells did have a DC-like ultrastructure, although the majority of these cells were identified as macrophages. The DC-like cells were characterized by poorly developed lysosomal structures and an absence of phagocytic vesicles. It was concluded that the normal rat PDL is equipped with heterogeneous populations of macrophages with regional variations in density. The DC-like cells may function as antigen-presenting cells.

Animals↗
PubMed1998

Expression of lectin-like oxidized low density lipoprotein receptor-1 in human and murine macrophages: upregulated expression by TNF-alpha.

Uptake of oxidized low density lipoprotein (Ox-LDL) and subsequent foam cell transformation have been implicated in early atherogenesis. Although multiple molecules, including class A and B scavenger receptors, have been identified as Ox-LDL receptors, additional receptors may also be involved in this process. Here, we provide evidence that lectin-like Ox-LDL receptor-1 (LOX-1), a novel Ox-LDL receptor initially identified in vascular endothelial cells, is also expressed in macrophages in humans and mice. Expression of LOX-1 can be induced after macrophage-like differentiation in vitro in human peripheral blood monocytes and the related cell line THP-1 cells. Furthermore, LOX-1 expression can also be detected in resident peritoneal macrophages, and can be upregulated by an inflammatory cytokine TNF-alpha. These results suggest that LOX-1 in macrophages may play an important role in Ox-LDL uptake and subsequent foam cell formation in this cell type.

Animals↗
PubMed2001

Localization and roles of CD44, hyaluronic acid and osteopontin in IgA nephropathy.

An important function of CD44 is to act as a cellular receptor for hyaluronic acid and osteopontin. Cell-matrix interactions mediated by the CD44/hyaluronic acid receptor-ligand pair are involved in the regulation of leukocyte migration and activation. Osteopontin is a molecule associated with cell adhesion and migration and functions through binding to CD44. This study examined whether CD44, hyaluronic acid and osteopontin participate in the progression of IgA nephropathy. CD44 was expressed in mesangial cells, crescents, tubular cells and interstitial infiltrating cells in areas of tubulointerstitial injury. Hyaluronic acid was deposited in the capillary tuft of adhesion, crescents and the periglomerular area, and around damaged tubules. Osteopontin was expressed in tubular cells and interstitial infiltrating cells in areas of tubulointerstitial injury. The glomerular and interstitial deposition of hyaluronic acid correlated with the glomerular and interstitial expression of CD44. The interstitial expression of CD44 correlated with the interstitial expression of osteopontin. The expression of both CD44 and osteopontin in the interstitium correlated with the extent of tubulointerstitial damage. The expression of CD44 in the interstitium correlated with the severity of chronic glomerular lesions. The glomerular and interstitial CD44 and hyaluronic acid expression correlated with proteinuria, and interstitial CD44 and hyaluronic acid expression correlated with creatinine clearance rate. In summary, this study suggests that CD44 participates in the progression of IgA nephropathy by binding hyaluronic acid and osteopontin.

Adolescent↗
PubMed2002

CD14 expression by activated parenchymal microglia/macrophages and infiltrating monocytes following human traumatic brain injury.

The immune response in the central nervous system (CNS) is under tight control of regulatory mechanisms, resulting in the establishment of immune privilege. CNS injury induces an acute inflammatory reaction, composed mainly of invading leukocytes and activated microglial cells/macrophages. The generation of this robust immune response requires binding of receptors such as CD14, a pattern recognition receptor of the immune system. CD14, a surface molecule of monocytic cells, is up-regulated after monocyte stimulation and is involved in cellular activation. To examine CD14 expression in human brain lesions we investigated sections of brains obtained at autopsy from 25 cases following closed traumatic brain injury (TBI) and 5 control brains by immunohistochemistry. Detection of CD14 in controls demonstrated constitutive expression by perivascular cells, but not in parenchymal microglial cells, equivalent to known expression pattern of ED2 in rats. Following TBI, numbers of CD14(+) cells in perivascular spaces and in the brain parenchyma increased in parallel within 1-2 days, both at the lesion and in adjacent perilesional areas. The number of CD14(+) cells in perivascular spaces and in the brain parenchyma reached maximum levels within 4-8 days and remained elevated until weeks after trauma. In contrast to activated parenchymal microglia/macrophages, resting parenchymal microglial cells lacked CD14. Thus, early CD14 expression constitutes an essential part of the acute inflammatory CNS response following trauma.

Adolescent↗
PubMed2004

Diversity in phenotype and steroid hormone dependence in dendritic cells and macrophages in the mouse uterus.

The dendritic cells and related antigen-presenting cells (APCs) that activate lymphocytes for acquired immunity in the female reproductive tract are not well characterized. The aim of the present study was to examine heterogeneity among uterine APCs in mice and, specifically, to determine whether phenotypically and functionally distinct subpopulations of dendritic cells and macrophages can be identified. Using immunohistochemistry, abundant cells expressing APC-restricted molecules major histocompatibility complex (MHC) class II, F4/80, class A scavenger receptor, macrosialin, and sialoadhesin were evident in estrous mice. Cells expressing the costimulatory molecule B7-2 were rarely observed. Flow cytometric analysis revealed three subpopulations of uterine APCs. Undifferentiated macrophages were F4/80-positive (+), MHC class II-negative (-) cells, of which 70-80% expressed CD11b, but few expressed class A scavenger receptor, macrosialin, or sialoadhesin. Mature macrophages were F4/80+/MHC class II+ cells, of which approximately 50% expressed CD11b, class A scavenger receptor, macrosialin, and sialoadhesin. Uterine dendritic cells were F4/ 80-/MHC class II+ cells, with stimulatory immunoaccessory function relative to uterine macrophages and heterogeneous expression of dendritic markers 33D1, DEC205, CD11c, and CD1. Experiments in ovariectomized mice showed that undifferentiated macrophages were steroid hormone dependent but that mature macrophages and dendritic cells persisted after depletion of ovarian steroid hormones, although with altered phenotypes. In summary, our findings identify three discrete populations of APCs inhabiting the murine uterus and suggest that both mature macrophages and dendritic cells differentiate from undifferentiated macrophage precursor cells. Plasticity in the ontogenetic and functional relationships between uterine dendritic cells and macrophages likely is critical in regulating immune responses conducive to reproductive success.

Animals↗
PubMed1998

Coexpression of collagens and collagen-binding heat shock protein 47 in human diabetic nephropathy and IgA nephropathy.

The mechanism of structural changes of the kidney in human diabetic nephropathy (DN) and IgA nephropathy (IgAN) is not yet completely known, but excessive deposition of extracellular matrix (ECM), including various collagens, may be crucial to this process. Heat shock protein (HSP) 47 has been identified as collagen-binding stress protein, shown to have a specific role in the intracellular processing of procollagen molecules during collagen assembly. To determine whether increased deposition of collagens in human DN and IgAN is related to HSP47, we investigated the expression of HSP47 in renal biopsy and autopsy sections obtained from 22 DN and 45 IgAN patients. Five renal biopsy specimens, diagnosed as minor glomerular abnormalities, were simultaneously studied as controls. Monoclonal antibodies specific for HSP47, type III collagen and type IV collagen were used to assess the relative expression of their proteins in paraffin-embedded renal sections by immunohistochemistry. Increased deposition of collagens was closely related to the sclerotic activity of the disease process in DN and IgAN; increased deposition of collagens was often present in relation to a strong expression of HSP47, a stress protein known to regulate collagen synthesis/assembly. By double immunostaining, we found colocalization of collagens and their molecular chaperone HSP47 in the sclerotic glomeruli and tubulointerstitium in DN and IgAN. Our results strongly support a pathologic role for HSP47 in both these diseases and that increased levels of HSP47 may play an important role in the excessive assembly of collagens resulting in glomerulosclerosis and interstitial fibrosis found in DN and IgAN patients.

Actins↗
PubMed1999

Effects of transpupillary thermotherapy on immunological parameters and apoptosis in a case of primary uveal melanoma.

Transpupillary thermotherapy (TTT) is a new treatment modality for uveal melanoma. We studied whether application of TTT influences the immunogenicity of the tumour cells in vivo or the expression of molecules related to apoptosis. Immunohistochemistry using monoclonal antibodies directed against HLA molecules, HMB45, P53, Fas ligand (FasL), Fas, Bcl-2 and tumour-infiltrating cells was applied to sections of an enucleated eye containing a uveal melanoma that received TTT 1 week before enucleation. The innermost part of the tumour which had been exposed directly to the laser treatment showed no staining for HLA antigens, nor for Fas or FasL epitopes. The intermediate part of the tumour showed a wet necrosis and HLA expression similar to the expression in the peripheral tumour. A large number of macrophages were observed in the necrotic as well as the intact tumour tissue, especially bordering the wet necrotic area. FasL and Bcl-2 were only expressed in the viable, outer part of the tumour. This immunological evaluation of one case of uveal melanoma treated with TTT revealed that TTT may not only have a direct destructive effect on the primary tumour, but may also influence the immunogenicity of uveal melanoma cells, induce infiltration of macrophages into the tumour, and induce apoptosis. The presence of many macrophages suggests that they play a role in the removal of the TTT-treated tumour tissue by phagocytosis.

Adult↗