The foetal macrophage of the human placenta.
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Female↗
Biomedical subjects
M Castellucci
Publications and source records attributed to M Castellucci.
Extracellular matrix proteins in colorectal carcinomas. Expression of tenascin and fibronectin isoforms.
BACKGROUND: Interactions of tumor cells and extracellular matrix (ECM) components are crucial determinants of tumor cell spreading and metastatic activity. Particularly tenascin (TN) as a member of the adhesion modulating family of ECM and its alternatively spliced isoforms became the matter of interest in ECM changes associated with malignancy. EXPERIMENTAL DESIGN: We analyzed the composition of the stromal- and basement membrane-associated ECM of colorectal adenomas and carcinomas using indirect immunofluorescence. Tenascin was investigated by immunoblot of snap frozen tumor specimens. RESULTS: Fibronectin (FN), TN, and chondroitin sulfate proteoglycan were the major components of the tumor stroma. Normal basement membrane components like laminin (LM), collagen type IV, and heparan sulfate proteoglycan were down-regulated. In the center of the tumor, tumor glands were surrounded by discontinuous basement membranes. At the tumor-host interface and in solid, poorly differentiated tumors, no immunoreactivity with normal basement membrane components was found. However, in cases with pericellular anti-LM staining, LM immunoreactivity was also found at the tumor-host interface. An alternatively spliced isoform of TN with a molecular weight of 330 kDa was found in seven of 15 carcinomas. In four of these cases, an alternatively spliced isoform of FN containing the ED-B segment was present. CONCLUSIONS: The coexpression of alternative splicing of FN and TN suggests that there may be common regulation mechanisms. The matrix composition found in the present study resembles that of healing wounds and probably favors the invasive spread of tumor cells.
Adenoma↗
Immunohistochemistry of carbonic anhydrase in human placenta and fetal membranes.
The localization of human carbonic anhydrase (CA) isoenzymes HCA I, HCA II, and rat CA II have been studied in human umbilical cord, chorion laeve including amnion and placenta from first and second trimester and also from term pregnancies. Detection techniques of immunofluorescence and immunoperoxidase were used in cryostat and paraffin sections. Both isoenzymes were found in the villous syncytiotrophoblast throughout pregnancy. HCA I staining patterns in the villous endothelium were highly variable whereas increasing immunoreactivity levels of endothelial HCA II were detected as pregnancy advances. The extravillous cytotrophoblast showed generally weaker levels of immunoreactivity. In amnionic epithelium of membranes, chorionic plate and umbilical cord, higher activities for HCA I, HCA II and rat CA II were found than in all other localizations. Our findings emphasize the importance of enzyme mediated bicarbonate/CO2 removal from the feto-placental unit as opposed to simple bicarbonate diffusion or carrier mediated transport. As effective transfer routes should be considered not only umbilical cord--placental villi--intervillous space, but also fetal kidney--amnionic fluid--amnion--uterine vessels.
Amnion↗
Immunohistochemical localization of serine-protease inhibitors in the human placenta.
Proteases and their inhibitors play a pivotal role in developmental and differentiative processes. In the present report we investigated the immunohistochemical localization of alpha 1-antitrypsin, alpha 1-antichymotrypsin and inter-alpha-trypsin inhibitor in first trimester as well as in term human placentas. For this purpose polyclonal antibodies against these serine-protease inhibitors were used. All inhibitors were expressed in the villous syncytiotrophoblast of first and last trimester placentas. Placental fibrinoid was positively stained for alpha 1-antitrypsin and inter-alpha-trypsin inhibitor throughout gestation. alpha 1-Antitrypsin and alpha 1-antichymotrypsin showed a strong immunostaining in the Hofbauer cells (first trimester and full term placentas). Extravillous cytotrophoblast was negative for the three protease inhibitors throughout gestation. The presence of the three inhibitors in the syncytiotrophoblast suggests a role in coagulative, invasive and immunomodulatory processes. Fibrinoid, staining for alpha 1-antitrypsin and inter-alpha-trypsin inhibitor, could also have an important immunoprotective function. The presence of protease inhibitors in the Hofbauer cells suggests an involvement of these cells in villous remodelling and differentiative processes.
Alpha-Globulins↗
Immunohistochemistry of two different types of placental fibrinoid.
The structure and composition of human placental fibrinoid were studied on cryostat and paraffin sections and by transmission electron microscopy as well as immunohistochemistry using antibodies directed against fibrin, fibronectin isoforms, collagens IV and VI, laminin and tenascin. The findings suggest two structurally and immunohistochemically different subtypes of fibrinoid: fibrin-type fibrinoid and matrix-type fibrinoid. Fibrin-type fibrinoid was characterized by immunoreactivity for fibrin and cellular fibronectin, including the ED-A sequence. Immunostaining for all other extracellular matrix molecules was negative. Ultrastructurally, this fibrinoid subtype consisted of a meshwork of fibers with 20-nm cross striation typical of fibrin. Fibrin-type fibrinoid never contained extravillous trophoblast cells. It is therefore primarily a blood clot product derived from maternal and fetal blood. In contrast, matrix-type fibrinoid showed virtually no evidence of fibrin; it was immunopositive for extracellular matrix molecules such as the fibronectins, particularly oncofetal fibronectin (containing the ED-B sequence), collagen IV, laminin and tenascin. Oncofetal fibronectin, which was neither expressed in fibrin-type fibrinoid nor in the villous stromal core, seemed to be a specific marker for matrix-type fibrinoid. Single or clustered nonproliferative extravillous trophoblast cells were embedded within the matrix molecules. It is very likely that these cells secrete the matrix in a non-polarized fashion. Fibrin-type fibrinoid would appear to be involved in shaping the intervillous space and in replacing damaged syncytiotrophoblast acting as a transport and immune barrier. Matrix-type fibrinoid, as a secretory product of the extravillous trophoblast, should be discussed in context with the invasive properties of this cell population.
Cell Adhesion Molecules, Neuronal↗
Differentiation and proliferation patterns in human trophoblast revealed by c-erbB-2 oncogene product and EGF-R.
It is well known that growth factors and proto-oncogenes play a pivotal role in organogenesis as well as in tumor development. The human placenta is a rapidly growing organ which shares some aspects with malignant tumors. We have studied the expression of epidermal growth factor receptor (EGF-R) and the receptor encoded by the c-erbB-2 proto-oncogene in first- and third-trimester human placentas. We compared these expression patterns with that of the proliferation marker Ki-67. By immunohistochemistry, EGF-R was intensively expressed in the villous cytotrophoblast in the first trimester. The apical plasma membrane of the syncytium was weakly stained. In placental villi from the third trimester the reaction product for EGF-R was most intense in single villous cytotrophoblastic cells and along the apical plasma membrane of the syncytium, whereas the basal plasma membrane was much less stained. C-erbB-2 protein product was expressed in the first and third trimesters along the apical membrane of the syncytiotrophoblast. Concerning the extravillous trophoblast in cell islands and cell columns, EGF-R was expressed in the cells proximal to the villous stroma whereas the distal cells were c-erbB-2 positive. The Ki-67 antibody revealed the proliferative character of the villous cytotrophoblast and of the EGF-R-positive extravillous trophoblast. In contrast, most of the c-erbB-2-positive cells were Ki-67 negative. By in situ hybridization, c-erbB-2 transcripts were found in all types of villous and extravillous trophoblast, including those that did not express c-erbB-2 protein product. Our data indicate that EGF-R expression is strongly related to the proliferative trophoblast and, with advancing pregnancy, to the differentiated villous trophoblast.off contrast, expression of c-erB-2 protein product occurs only in more advanced stages of trophoblast differentiation, although transcripts of c-erbB-2 are found in both proliferative and differentiated trophoblast. In addition, the coexpression of EGF-R and c-erbB-2 protein product in the syncytiotrophoblast suggests their involvement in complex regulation of hormones and growth factors.
Cell Division↗
Expression of intermediate filaments and actins in human dental pulp and embryonic dental papilla.
The localization of different cytoskeletal proteins (keratin, vimentin, desmin, actin, and alpha-smooth muscle actin) was examined by immunohistochemistry in normal human adult dental pulp and compared with dental papilla of tooth germs. Keratin and actin were localized in enamel organ. Vimentin and actin were observed in the dental papilla and in the adult dental pulp. Desmin and alpha-smooth muscle actin were present only in the vessel walls. These data are discussed paying particular attention to the origin and the peculiar functional characters of the dental papilla and pulp.
Actins↗
The human placenta: a model for tenascin expression.
Tenascin is a large glycoprotein of the extracellular matrix. Previous reports have demonstrated that it is associated with epithelial-mesenchymal interfaces and is expressed during embryonic and tumour development, wound healing, cell proliferation and it may be involved in immunomodulation. The human placenta shows numerous features related to these aspects. We have investigated the presence of tenascin in the human placenta throughout pregnancy by immunohistochemistry. We used monoclonal (mAb) and polyclonal (pAb) antibodies to tenascin, a mAb to fibrin, a pAb to fibrinogen, and the mAb Ki-67 as proliferation marker. Tenascin was highly expressed in the mesenchymal villi which are considered the basis of growth and differentiation of the villous trees. Moreover, fibrinoid deposits at the surfaces of the villous trees were always separated from the fetal stroma by tenascin. The stroma of villi encased in fibrinoid was also positive for tenascin. This glycoprotein was also expressed in the villous stroma directly apposed to cell islands and cell columns. In the proximal portions of both epithelial structures, cytotrophoblast was Ki-67 positive. These data show that tenascin is expressed during the development of the placenta, particularly in the mesenchymal villi, cell islands and cell columns. These structures are considered to be the proliferating units of the villous trees. Tenascin underlying fibrinoid deposits suggests that it also participates in repair mechanisms. Thus, in the human placenta tenascin expression can be correlated with villous growth, cell proliferation, and fibrinoid deposition. Its role in immunoprotection of fetal tissues in areas where syncytiotrophoblast as barrier is missing or damaged is discussed.
Cell Adhesion Molecules, Neuronal↗
The development of the human placental villous tree.
The present investigation was undertaken in order to achieve a better understanding of the dynamics of placental villous differentiation. Villous trees from human placentas from different stages of pregnancy (first trimester to full term) were isolated and studied by light microscopy and scanning electron microscopy. For light microscopy the trees were serially sectioned and two-dimensionally reconstructed. For scanning electron microscopy complete villous trees or freeze-cracked villi were studied. The most important finding was that the mesenchymal villi are continuously newly formed out of the trophoblastic sprouts throughout pregnancy. Because of this they exist in all stages of pregnancy and have to be considered the basis for growth and differentiation of the villous trees. In the first two trimesters they are the forerunners of the immature intermediate villi, whereas in the last trimester the mesenchymal villi are transformed into mature intermediate villi. The immature intermediate villi formed during the first two trimesters are developmental steps towards the stem villi. On the other hand, the mature intermediate villi, which only are developed during the last trimester, produce numerous terminal villi. The latter are not active outgrowths caused by proliferation of the trophoblast, but rather passive protrusions induced by capillary coiling due to excessive longitudinal growth of the fetal capillaries within the mature intermediate villi.
Cell Differentiation↗
Extracellular matrix influences hormone and protein production by human chorionic villi.
Increasing evidence confirms that the extracellular matrix greatly influences cell behaviour and function. Collagen and fibrin are in contact with trophoblast throughout pregnancy. To investigate whether these two matrices influence hormone production by the trophoblast, explants from first-trimester chorionic villi were cultured for up to 30 days either a) in medium with agitation, b) embedded in type-I collagen (three-dimensional gels), or c) embedded in fibrin (three-dimensional gels). The supernatant culture medium was changed every 48 h and tested by radioimmunoassay for hCG, progesterone and pregnancy-associated plasma protein A. In addition, after 3, 7, 15, and 30 days of culture villi were fixed and studied by light and electron microscopy. Embedding in the extracellular matrix showed higher and longer-lasting production rates of all measured products and superior structural preservation as compared to cultures with agitation. Collagen matrix proved to be superior to fibrin. As established by several tests, this difference was neither due to thrombin used to polymerize fibrinogen, nor to differences in the diffusion rates through the two different matrices used. We conclude that extracellular matrix, particularly collagen, influences the synthesis of trophoblastic products. Embedding of the villous explants in three-dimensional gels constitutes a new method for long-term cultures of chorionic villi.
Chorionic Gonadotropin↗
Bowes human melanoma cell line. An immunocytochemical study.
Bowes human melanoma cell line was investigated immunocytochemically to localize S-100 protein, HMB-45 and intermediate filament proteins. The majority of the cells showed strong positive staining with antibodies directed against S-100 protein, HMB-45 and vimentin filaments. Antibodies directed against the other cytoskeletal proteins failed to show any reactivity. These findings suggest that this transformed cell line does not dedifferentiate in culture and continues to express the specific antigens of human melanoma cells. Thus, Bowes cell line provides a useful model for studying the cellular biology and pathology of malignant melanoma.
Humans↗
Isolation and characterization of Hofbauer cells from human placental villi.
Hofbauer cells are a major cell type of the human placental villous core and they are particularly numerous at the beginning of pregnancy. In the present study we describe a method suitable to obtain HC suspensions in a highly purified form. These suspensions have been analyzed for surface markers using a battery of monoclonal antibodies. Of all the surface markers used, Hofbauer cells were only positive for 4F2, LeuM2 and LeuM3 monoclonals which mainly detect cells of the monocyte-macrophage lineage. Hofbauer cells were consistently negative for HLA-DR antigens, C3bR and T- or B-cell markers. Hofbauer cells appeared capable of phagocytosing latex beads, adhering to and spreading over plastic surface and secreting lysozyme. In contrast, they failed to originate an efficient respiratory burst in response to appropriate stimulation. Hofbauer cells were positive for ANAE with a perinuclear localization of the enzyme activity, but consistently negative for peroxidase. These observations suggest that they share a number of features with cells of the monocyte-macrophage lineage and yet have some distinctive properties.
Chorionic Villi↗
S-100 protein localization in human adult dental pulp.
The pulp of third molar teeth was examined by immunofluorescence and immunoperoxidase using a specific antibody to detect S-100 protein-labelled cells. There was a strong positive reaction in macrophages and in Schwann cells ensheathing axons. The other cells within the pulp were negative.
Adult↗
Fetal vasculogenesis and angiogenesis in human placental villi.
Placental villi of 5 exactly defined early human specimens ranging from day 21 post conception (p.c.) until day 42 p.c. and from an additional 43 specimens from about 5 to 40 weeks menstrual age have been analyzed ultrastructurally with regard to fetal vasculogenesis and angiogenesis. The following results were obtained: The first cells differentiating at day 21 p.c., probably originating from mesenchymal precursors, are macrophage-like cells. At almost the same time, mesenchymal cells transform into haemangioblastic cell cords which are the forerunners of the capillary endothelium and haematopoietic stem cells. A third cell population related to the fetal circulatory system and derived from the mesenchymal cells are presumptive pericytes. Capillary formation takes place by the aggregation of haemangioblastic cells which are attached to each other by intercellular junctions. The lumen is formed by the dehiscence of the intercellular clefts. A capillary basal lamina cannot be detected earlier than in the last trimester. In this last period of gestation, fetal villous angiogenesis takes place by the proliferation of the existing endothelium and pericytes rather than via haemangioblastic cells.
Blood Vessels↗
The Hofbauer cells of the human placenta: morphological and immunological aspects.
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Female↗
Phorbol ester stimulates macrophage invasion of fibrin matrices.
Macrophages migrate through a fibrin-rich extracellular matrix in chronic inflammation, wound healing, and other pathophysiological processes. To investigate the factors that might influence the ability of mononuclear phagocytes to invade fibrin matrices, we cultured macrophage-like P388D1 cells as well as resident and thioglycollate-elicited mouse peritoneal macrophages on three-dimensional fibrin gels, and we examined the effect of agents known to stimulate a variety of macrophage functions, including the production of fibrinolytic enzymes. Cells grown on fibrin gels under control conditions, as well as cells treated with either bacterial lipopolysaccharide or concanavalin A, remained confined to the gel surface. In contrast, the tumor promoter 4 beta-phorbol 12-myristate 13-acetate (PMA) induced both P388D1 cells and peritoneal macrophages to invade the underlying fibrin matrix. The invasive behavior of PMA-treated P388D1 cells was not affected by protease inhibitors of various specificities. These results demonstrate that certain exogenous signals can profoundly modify the ability of macrophages to migrate through fibrin matrices.
Animals↗
The elasmobranch renal corpuscle: fine structure of Bowman's capsule and the glomerular capillary wall.
The fine structure of the renal corpuscle of the marine elasmobranch fish, the little skate (Raja erinacea), and two species of dogfish sharks, the spiny dogfish (Squalus acanthias) and the smooth dogfish (Mustelus canis), was studied by light microscopy and by transmission (thin sections, freeze-fracture replicas) and scanning electron microscopy. Bowman's capsule was lined by ciliated cells, similar to those of the first part of the tubule, at the urinary pole and squamous cells in the zone between urinary and vascular poles. At the vascular pole the visceral epithelial cells had some closely apposed cuboidal cell bodies with a few processes inserted along the basement membrane, but foot processes were absent. These cuboidal cells were continuous with podocytes, which had primary, secondary and tertiary processes from which the pedicels arose. An inconsistently present slit membrane bridged the pedicels at varying distance from the urinary space. Small maculae and large fasciae occludentes joined the podocytes and/or their processes among which gap junctions were observed. In the skate kidney, the podocyte plasma membrane facing the basement membrane contained orthogonal arrays of particles. The epithelial basement membrane of the glomeruli in all elasmobranchs was consistently thick. The mesangial cells were numerous and partially enveloped in a basement membrane; their long processes almost completely circumscribed the capillary walls. The mesangial matrix was abundant and consisted of loosely arranged collagen fibrils, microfibrils and occasional anchoring fibrils. The endothelial cells had irregularly distributed fenestrations of various sizes and lay on their discontinuous basement membrane which was separate from that under the epithelial cells. The filtration apparatus resembles that of immature mammals and lower vertebrates.
Animals↗
Scanning electron microscopy of stromal cells of human placental villi throughout pregnancy.
Morphological changes in fixed stromal cells and Hofbauer cells were studied throughout pregnancy in different types of placental chorionic villi by scanning electron microscopy. In the mesenchymal villus the fixed stromal cells were characterized by thin cytoplasmic processes. Hofbauer cells exhibited blebs on their surface. Large sail-like processes with a crescent profile which surrounded well developed stromal channels and a small cell body typified the small reticulum cells of the immature intermediate villus. The Hofbauer cells here displayed blebs, microplicae and large lamellipodia. Short cytoplasmic expansions and a large cell body characterized the fibroblasts present inside the stem villus. Hofbauer cells were rare, having blebs or a few short lamellipodia. The mature intermediate villus contained small and large reticulum cells. The latter had a much larger cell body than the small ones and displayed a few short cytoplasmic processes partly delimiting narrow incomplete stromal channels. Occasional Hofbauer cells with small microplicae and/or blebs were present. The small reticulum cells and fibroblasts present in the terminal villus showed similar morphological features as above. However, the former exhibited less developed cytoplasmic extensions and therefore no stromal channels were observed. In the terminal villus, the morphology of the rare Hofbauer cells was similar to that found in the mature intermediate villus.
Chorionic Villi↗