Biomedical subjects

C B Underhill

Publications and source records attributed to C B Underhill.

At least 37 records · Page 2Linked to original sources

PubMed1994

CD44 can mediate the adhesion of platelets to hyaluronan.

CD44 represents a family of glycoproteins that are present on the surfaces of some types of lymphocytes, macrophages, and epithelial cells. In the present study, we have found that CD44 is also present on murine megakaryocytes and peripheral blood platelets as judged by immunohistochemical staining. Western blotting of platelet proteins indicated that this CD44 was predominantly of the 85-kD form. This form of CD44 also had the capacity to bind hyaluronan, because detergent extracts of platelets as well as intact platelets could bind soluble [3H]hyaluronan, and this property was blocked by antibodies directed against CD44. More importantly, isolated platelets could attach to the hyaluronan-containing extracellular matrix produced by cultured rat fibrosarcoma cells. This attachment took place in the absence of divalent cations and could be blocked by pretreating the rat fibrosarcoma cells with hyaluronidase or by the addition of an antibody to CD44. These results suggested that CD44 was responsible for the attachment of platelets to hyaluronan. Histochemical staining also showed that hyaluronan was present immediately beneath the endothelial cells of many blood vessels of various tissues, such as the dermis, lamina propria of the intestinal tract, the lungs, and the pericardium. Thus, it is possible that CD44 plays an important role in the attachment of platelets to the surface of exposed connective tissue after injury to endothelial cells.

Animals↗

PubMed1994

Binding and degradation of hyaluronan by human breast cancer cell lines expressing different forms of CD44: correlation with invasive potential.

In the present study, we examined a panel of human breast cancer cell lines with regard to their expression of CD44 and ability to bind and degrade hyaluronan. The cell lines expressed varying amounts of different molecular weight forms of CD44 (85-200 kDa) and, in general, those that expressed the greatest amounts of CD44 were the most invasive as judged by in vitro assays. In addition, the ability to bind and degrade hyaluronan was restricted to the cell lines expressing high levels of CD44, and both these functions were blocked by an antibody to CD44 (Hermes-1). Moreover, the rate of [3H]hyaluronan degradation was highly correlated with the amount of CD44 (r = 0.951, P < 0.0001), as well as with the invasive potential of the cells. Scatchard analysis of the [3H]hyaluronan binding of these cells revealed the existence of significant differences in both their binding capacity and their dissociation constant. To determine the source of this deviation, the different molecular weight forms of CD44 were partially separated by gel filtration chromatography. In all cell lines, the 85 kDa form was able to bind hyaluronan, although with different affinities. In contrast, not all of the high molecular weight forms of CD44 had this ability. These results illustrate the diversity of CD44 molecules in invasive tumor cells, and suggest that one of their major functions is to degrade hyaluronan.

Blotting, Western↗

PubMed1994

Hyaluronan receptor (CD44) expression and function in human peripheral blood monocytes and alveolar macrophages.

CD44 glycoproteins are present on the surfaces of many hematopoietic cells and in some cases can bind hyaluronan, a major component of the extracellular matrix. In the present study, we have found that newly explanted human peripheral blood monocytes (PBMs) exhibit a major CD44 band of 85 kDa, whereas autologous alveolar macrophages (AM phi) express multiple isoforms ranging from 85 to 200 kDa. Within 4 h in culture, PBMs began expressing new CD44 isoforms of 120, 150, and 180 kDa. Newly explanted AM phi specifically bound [3H]hyaluronan (135 cpm/microgram protein), but newly explanted PBMs did not. However, in vitro cultured PBM progressively acquired the ability to bind [3H]hyaluronan and exhibited specific binding of hyaluronan similar to that of AM phi (113 cpm/microgram protein) after 4 days in culture. In both case, the binding of [3H]hyaluronan was specifically inhibited by the addition of monoclonal antibody directed against CD44. AM phi readily degraded [3H]hyaluronan and reached a plateau after 4 days in culture (115 cpm/microgram protein). Newly explanted PBM exhibit no hyaluronan degradation and only a small degradative activity after 4 days in culture (6 to 11 cpm/microgram protein). Thus, CD44 expression and function appear to change as PBM mature in vitro resembling more that found in AM phi.

Adult↗

PubMed1994

Distribution of hyaluronan in the epiphysial growth plate: turnover by CD44-expressing osteoprogenitor cells.

In the present study, we have examined the distribution of both hyaluronan and its receptor, CD44, during the process of endochondral ossification in the mouse tibia. Histochemical staining revealed that a large amount of hyaluronan was present in the lacunae located in the zone of hypertrophy, but it was greatly reduced or absent from the zone of erosion. In addition, hyaluronan was present in the cytoplasm of osteoprogenitor cells located in the zone of erosion. These cells also expressed CD44 on their surfaces, as revealed by double-label immunohistochemistry. These results suggested that the osteoprogenitor cells may use CD44 to bind and internalize hyaluronan, and subsequently degrade it with lysosomal enzymes. To test this possibility, we examined the human cell line, MG-63, which closely resembles osteoprogenitor cells. These cells produced several different forms of CD44, as determined by western blotting (85, 116 and 150 kDa). In addition, the binding of isotopically labeled hyaluronan to detergent extracts of these cells was blocked by a monoclonal antibody to CD44. Similarly, the degradation of hyaluronan by these cultured cells was also inhibited by a monoclonal antibody to CD44. To determine if these cells could remove hyaluronan from the growth plate, the cells were cultured directly on top of thin sections of the epiphysial region of long bone. After 16 hours, the sections were stained for hyaluronan. The MG-63 cells removed significant amounts of hyaluronan present in the zone of hypertrophy, and this effect was blocked by an excess of soluble hyaluronan and by a monoclonal antibody to CD44.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Hyaluronan in the bovine ocular anterior segment, with emphasis on the outflow pathways.

PURPOSE: It has been postulated that glycosaminoglycans play a role in the regulation of outflow resistance. The purpose of these studies was to localize the distribution of hyaluronan (HA) in the anterior segments of bovine eyes to understand better the possible role of HA in the outflow pathway. METHODS: Eyes from four 2-week-old calves and four 1-year-old cows were examined using a biotinylated-hyaluronan binding protein to localize HA in tissue sections of the anterior segment of bovine eyes. Various fixations and microwave irradiation were compared. The vitreous body in each section served as a positive control. Sections treated with Streptomyces hyaluronidase were used to confirm specificity. RESULTS: No significant difference in distribution of HA was found between various fixations and between calves and cows. HA was found in subconjunctival connective tissue and in intercellular spaces of limbal and conjunctival epithelium, but not in corneal epithelium. Staining was sometimes found on the surface of the corneal epithelium and endothelium, as well as on the conjunctival epithelium. No staining was found within the corneal stroma. There was HA in iris stroma, but not in the root of the iris or ciliary body stroma. HA was present in the anterior, nonfiltering part of the trabecular meshwork (TM) and surrounding collector channels and blood vessels in the sclera; to a lesser extent, it was present in the juxtacanalicular region of the TM. HA was detectable neither within trabecular beams nor filling the intertrabecular spaces. Strong staining was found, however, in the nerve bundles in the angle region. Staining for HA in vitreous was invariably positive, and in Streptomyces hyaluronidase-treated sections it was negative. CONCLUSION: HA was not uniformly distributed in the bovine TM. The distribution of HA in the flow pathway of the aqueous outflow system indicates that only a small fraction of the HA found in biochemical analyses of the bovine meshwork is located in the region where the flow resistance is thought to reside.

Animals↗

PubMed1993

CD44 positive macrophages take up hyaluronan during lung development.

In the present study, we examined the expression and distribution of both hyaluronan and its cell-surface receptor (CD44) during lung development in the mouse. Hyaluronan was detected by a specific binding probe, termed b-PG, which is a biotinylated mixture of proteoglycan and link protein from cartilage. Using this probe in an enzyme-linked assay, the amount of hyaluronan in relation to protein content was found to decrease as lung development progressed. In addition, histochemical staining of the embryonic lungs revealed that during early stages, relatively large amounts of hyaluronan were present in the interstitium. However, as development progressed, much of this was lost, and in the adult, hyaluronan was restricted to the regions surrounding the major blood vessels, bronchi, and bronchioles. In contrast to hyaluronan, the amount of CD44 increased as a function of development, as determined by the rat monoclonal antibody, KM-201. Histochemical staining with this antibody showed that the receptor was primarily associated with macrophages and to a lesser extent with adult bronchial and bronchiolar epithelium, vascular smooth muscle, and endothelial cells. As development progressed, the macrophages expressing CD44 increased in number, and this increase was temporarily correlated with the decrease in hyaluronan content. In addition, histochemical staining revealed that some of these macrophages contained hyaluronan in their cytoplasm, suggesting that macrophages had internalized hyaluronan from the extracellular matrix. This possibility was further supported by the fact that when newborn mice were injected with the KM-201 monoclonal antibody, which blocks the interaction between hyaluronan and the receptor, the number of hyaluronan-containing macrophages in the lungs decreased while the concentration of hyaluronan increased. Taken together, these results suggest that macrophages can internalize hyaluronan during lung development and could possibly play a significant role in its removal.

3T3 Cells↗

PubMed1993

Hyaluronan is inversely correlated with the expression of CD44 in the dermal condensation of the embryonic hair follicle.

Previously, we have shown that CD44 (the hyaluronan receptor) was involved in the degradation of hyaluronan. In the present study, we examined the distribution of CD44 and hyaluronan in the skin of embryonic and mature mice. During embryonic development, CD44 was prominently expressed by the condensed mesenchymal cells involved in the formation of the hair follicles, but was absent from the surrounding interstitial cells. The cells of the dermal condensation expressed CD44 throughout the development of the hair follicle; however, once the hair follicle reached maturity, the mesenchymal cells of the dermal papilla no longer expressed this molecule. In contrast to the above, the distribution of hyaluronan was reversed from that of CD44. Hyaluronan was widespread throughout the embryonic dermis, but was conspicuously absent from the regions of the dermal condensation. This arrangement persisted through the development of the hair follicle; however, in the mature hair follicle, hyaluronan reappeared in the dermal papilla. Thus, in the embryonic dermis, the expression of CD44 and hyaluronan were complementary to each other. However, in the adult skin, only minor changes were detected in the levels of CD44 and hyaluronan associated with the cells of the dermal condensation during the hair cycle. When organ cultures of embryonic mouse skin were treated with Streptomyces hyaluronidase, the interstitial mesenchymal cells became compacted, indicating that the removal of hyaluronan leads to the condensation of these cells. The results of this study are consistent with the hypothesis that the expression of CD44 by the inductive mesenchymal cells allows them to degrade hyaluronan in a localized region, leading to formation and maintenance of the dermal condensation.

Aging↗

PubMed1992

Localization and synthesis of hyaluronic acid in the cumulus cells and mural granulosa cells of the preovulatory follicle.

Mural and cumulus granulosa cells synthesize hyaluronic acid (HA) and expand in vitro in response to follicle-stimulating hormone and a soluble factor(s) produced by fully grown oocytes. In the present study we examined HA synthesis and extracellular matrix organization by the two cell populations in vivo during the preovulatory period. After injection of human chorionic gonadotropin into pregnant mares' serum gonadotropin-primed animals, a progressive increase in HA synthesis was observed by the cumulus cell-oocyte complex (COC), and by the mural granulosa cells adjacent to the antrum (antral granulosa cells). The outermost layers of mural granulosa cells (peripheral granulosa cells) did not synthesize HA. Net HA synthesis was approximately 4 pg/cell for COCs isolated after full expansion induced either in vivo or in vitro, whereas the total HA content and cell number in the ovulated COC (approximately 11 ng HA and approximately 3000 cells per COC) were about threefold higher than for COCs expanded in vitro (approximately 4 ng HA and approximately 1000 cells per COC). The increased cell content of ovulated COCs appears to be primarily the result of inclusion of proximal mural granulosa cells which synthesize HA in response to the oocyte factor(s) and become incorporated in the expanded COC extracellular matrix mass. Media conditioned by oocytes enclosed in the cumulus cell mass (intact COCs) contained only 10-20% of the HA-stimulatory activity of media conditioned by an equal number of isolated oocytes when tested on mural granulosa cell cultures. Further, HA-stimulatory activity of media conditioned by isolated oocytes was dramatically reduced (approximately 70%) by preincubation for 5 hr with cumulus cells compared to preincubation in the absence of cells. The results suggest that differences in HA synthesis between subregions of membrana granulosa depend on a diffusion gradient of the oocyte factor(s).

Animals↗

PubMed1992

The hyaluronan receptor (CD44) participates in the uptake and degradation of hyaluronan.

The hyaluronan receptor belongs to the polymorphic family of CD44 glycoproteins, which have been implicated in a variety of cellular functions including adhesion to hyaluronan and collagen, the binding of lymphocytes to high endothelial cells during extravasation, and conferring metastatic potential to carcinoma cells. Here, we demonstrate that the receptor also participates in the uptake and degradation of hyaluronan by both transformed fibroblasts (SV-3T3 cells) and alveolar macrophages. These cells were incubated with isotopically labeled hyaluronan for various periods of time, and the extent of degradation was determined by either molecular-sieve chromatography or centrifugation through Centricon 30 microconcentrators. The macrophages degraded the hyaluronan at a faster rate than the SV-3T3 cells, which may reflect the fact that they contained a greater number of receptors. More importantly, in both cell types, the degradation of hyaluronan was specifically blocked by antibodies directed against the receptor. However, the receptor by itself did not have the ability to degrade hyaluronan, since preparations of SV-3T3 membranes containing the receptor did not break down hyaluronan. Subsequent experiments revealed that macrophages can internalize fluorescein-tagged hyaluronan, and this process was blocked by antibodies against the receptor. Furthermore, the subsequent degradation of hyaluronan was inhibited by agents that block the acidification of lysosomes (chloroquine and NH4Cl). Thus, the most likely explanation for these results is that the receptor mediates the uptake of hyaluronan into the cell where it can be degraded by acid hydrolases in lysosomes. The ability of cells expressing the receptor to degrade hyaluronan may be important during tissue morphogenesis and cell migration.

Ammonium Chloride↗

PubMed1992

A novel biotinylated probe specific for hyaluronate. Its diagnostic value in diffuse malignant mesothelioma.

Diffuse malignant mesotheliomas are known to secrete a large amount of hyaluronate, whereas adenocarcinomas produce predominantly neutral mucins. In the present study, we assessed the diagnostic usefulness of a new, highly specific and sensitive hyaluronate binding probe to discriminate between mesotheliomas and adenocarcinomas. We studied 33 mesotheliomas and 37 adenocarcinomas in order to establish specific diagnostic criteria for using the hyaluronate binding probe. Of the adenocarcinomas, only three showed significant positive staining for hyaluronate (8%). By contrast, all the mesotheliomas exhibited positive staining for hyaluronate. Furthermore, the staining reaction was classed as moderate or greater in 26 mesotheliomas (79%), thus suggesting the utility of this probe in the differential diagnosis of malignant mesothelioma versus adenocarcinoma. We conclude that strong cytoplasmic or membranous staining for hyaluronate is highly predictive of malignant mesothelioma. The hyaluronate binding probe should therefore be considered an important adjunct to be used in combination with electron microscopy and immunohistochemistry in the histologic diagnosis of diffuse malignant mesothelioma.

Adenocarcinoma↗

PubMed1992

Hyaluronan can be non-enzymatically linked to protein through an alkali sensitive bond.

To test for the presence of hyaluronan to protein linkages, both purified and unpurified preparations of hyaluronan were blotted onto nitrocellulose, and the adsorbed hyaluronan was detected using a biotinylated probe derived from cartilage. While purified hyaluronan did not adsorb to nitrocellulose, the unpurified hyaluronan from rat fibrosarcoma (RFS) cells and chick embryos did. This adsorption appeared to require the presence of protein, since it was inhibited by treatment with proteases. Furthermore, when hyaluronan from RFS cells was subjected to conditions which break most non-covalent bonds, it retained its ability to adsorb to nitrocellulose, suggesting that this hyaluronan was covalently bound to protein which mediated its adsorption to nitrocellulose. While this bond was resistant to acidic buffers, it was readily broken by alkaline buffers. Additional experiments demonstrated that when either purified [3H] hyaluronan or oligosaccharide fragments of hyaluronan were incubated with a variety of proteins, they slowly gained the ability to adsorb to nitrocellulose. However, this process could be blocked by the addition of low molecular weight amines or by reducing the [3H] hyaluronan with NaBH4. These results are consistent with the possibility that the reducing terminal of the hyaluronan reacts with amine groups of protein to form a Schiff base which then rearranges to a stable bond. Such a bond could account for the association of hyaluronan with the surfaces of RFS cells.

Adsorption↗

PubMed1990

Hyaluronate can function as a cell adhesion molecule and CD44 participates in hyaluronate recognition.

A cell adhesion model was previously used to select a series of monoclonal antibodies (mAbs), which were subsequently found to recognize CD44/Pgp-1. Interest in these reagents increased with the finding that they totally inhibited production of lymphoid or myeloid cells in long-term bone marrow cultures. Further investigation has now revealed that hyaluronate is a potential ligand for CD44 and that hyaluronate recognition accounts for the adhesion between B lineage hybridoma and stromal cells. The hybridoma cells adhered to hyaluronate-coated plastic wells as well as to monolayers of stromal cells. The adhesion in both cases was inhibited by treatment with hyaluronidases, and did not require divalent cations. Addition of exogenous hyaluronate also diminished binding of lymphoid cells to stromal cells. One of several mAbs to Pgp-1/CD44 was particularly effective at blocking these interactions. Since hyaluronate and Pgp-1/CD44 were present on both cell types, experiments were done to determine the cellular location of interacting molecules required for the adhesion process. Treatment of lymphoid cells with an anti-Pgp-1/CD44 antibody was more inhibitory than antibody treatment of the stromal cells. Conversely, hyaluronidase treatment of stromal cells reduced subsequent binding more than treatment of the lymphoid cells. Adhesive interactions that involve hyaluronate and CD44 could contribute to a number of cell recognition processes, including ones required for normal lympho-hemopoiesis.

Animals↗

PubMed1990

CD44 is the principal cell surface receptor for hyaluronate.

CD44 is a broadly distributed cell surface protein thought to mediate cell attachment to extracelular matrix components or specific cell surface ligands. We have created soluble CD44-immunoglobulin fusion proteins and characterized their reactivity with tissue sections and lymph node high endothelial cells in primary culture. The CD44 target on high endothelial cells is sensitive to enzymes that degrade hyaluronate, and binding of soluble CD44 is blocked by low concentrations of hyaluronate or high concentrations of chondroitin 4- and 6-sulfates. A mouse anti-hamster hyaluonate receptor antibody reacts with COS cells expressing hamster CD44 cDNA. In sections of all tissues examined, including lymph nodes and Peyer's patches, predigestion with hyaluronidase eliminated CD44 binding.

Amino Acid Sequence↗

PubMed1989

The interaction of hyaluronate with the cell surface: the hyaluronate receptor and the core protein.

Two distinct mechanisms are discussed by which hyaluronate interacts with the surfaces of cells: first, through a receptor which binds to hyaluronate with high affinity; and second, through a hydrophobic protein which is covalently linked to hyaluronate. The hyaluronate receptor is a transmembrane glycoprotein of Mr 85,000 which appears to interact with actin filaments of the cytoskeleton. It recognizes a sequence of six sugar residues of hyaluronate and also binds to chondroitin sulphate with a lower affinity. On the cell surface the receptors bind hyaluronate in cooperative fashion whereby two or more receptors can bind to the same molecule of hyaluronate, resulting in a high affinity. Immunohistochemical staining with a monoclonal antibody to the receptor indicates that it is present on epithelia, macrophages and other mononuclear phagocytes as well as some type of neurons. In epithelia the receptors presumably help to mediate cell attachment to the basement membrane which is often rich in hyaluronate. The receptor also appears to be preferentially expressed on proliferating epithelial cells and may serve as a marker for some types of carcinomas. Macrophages and related cells also have large amounts of the receptor, where it may serve in cell migration and/or in the homing of the cells to certain types of tissues. Recent studies have suggested that cell surface hyaluronate is covalently attached to a membrane-associated core protein. First, if cultured rat fibrosarcoma cells are fixed with glutaraldehyde the cell surface hyaluronate remains associated with the cells even under conditions expected to break non-covalent bonds. Second, when cell surface hyaluronate is partitioned with Triton X-114 a significant fraction is recovered in the hydrophobic phase, suggesting attachment to a hydrophobic protein. And finally, the binding of cell surface hyaluronate to nitrocellulose appears to be mediated through a covalent linkage to a protein.

Animals↗

PubMed1989

The hyaluronate receptor is preferentially expressed on proliferating epithelial cells.

In the present study, we have examined the distribution of the hyaluronate receptor as well as hyaluronate itself in a variety of adult tissues. The hyaluronate receptor was localized with a monoclonal antibody, termed K-3, while hyaluronate was localized using proteolytic fragments of cartilage proteoglycan. Staining with the K-3 monoclonal antibody revealed that the hyaluronate receptor was present in a variety of epithelia including the skin, cheek, tongue, esophagus, vagina, intestines, oviduct, and bladder. However, it was notably absent from epithelial cells of the cornea and stomach as well as from endothelial cells of blood vessels. When present, the hyaluronate receptor was preferentially located in regions of active cell growth, such as in the basal layers of stratified epithelium and at the base of the crypts of Lieberkuhn in intestinal epithelium. A similar phenomenon was observed in cultured 3T3 cells. Cultures of 3T3 cells that were actively proliferating were found to have greater amounts of the receptor than their nonproliferating counterparts. When the various tissues were examined for hyaluronate, it was found to have a widespread distribution, being present in most of the basement membranes and between the cells in stratified epithelium. Indeed, in many cases, the distribution of hyaluronate closely paralleled that of the hyaluronate receptor. These results suggest that the interaction between hyaluronate and its receptor is involved in cell-to-substratum adhesion.

Animals↗

PubMed1988

Hyaluronate appears to be covalently linked to the cell surface.

The purpose of this study was to examine the nature of the linkage between cell-surface hyaluronate and the plasma membrane. To accomplish this, rat fibrosarcoma cells were cultured in the presence of [3H]-acetate to isotopically label the hyaluronate, and then fixed with glutaraldehyde, which cross-links proteins but does not react directly with hyaluronate. The glutaraldehyde fixation stabilized the cells so that they could be manipulated in ways which would otherwise destroy cells. The fixed cells were then subjected to various treatments, and the amount of hyaluronate remaining on the cell surface was assayed via exhaustive digestion with Streptomyces hyaluronidase. Using this technique, we found that 1) cell-surface hyaluronate was quite stable for extended periods of time even in the presence of a large excess of non-labeled hyaluronate; 2) 4 M guanidine HCl and detergents did not extract a significant portion of cell-surface hyaluronate; 3) solutions of varying ionic strength (0-1 M NaCl) had no effect on the retention of hyaluronate; 4) the cell coat was stable in the range of pH 4-11, but outside this range a significant amount of hyaluronate was released; and 5) treatment with proteases released cell-surface hyaluronate. These results are consistent with the possibility that hyaluronate is covalently linked to a protein associated with the plasma membrane. Further support for this model came from experiments with the detergent Triton X-114, which can be used to separate soluble proteins from hydrophobic proteins. When nonfixed rat fibrosarcoma cells were extracted with this detergent and then partitioned by centrifugation, approximately 30 times as much hyaluronate was present in the detergent fraction which contained the hydrophobic proteins, as compared to the extracts pretreated with trypsin prior to phase separation. Again, these results suggest that cell-surface hyaluronate is directly linked to a hydrophobic core protein intercalated in the plasma membrane.

Animals↗

PubMed1988

Aggregation of macrophages and fibroblasts is inhibited by a monoclonal antibody to the hyaluronate receptor.

To examine the role of the hyaluronate receptor in cell to cell adhesion, we have employed the K-3 monoclonal antibody (MAb) which specifically binds to the hyaluronate receptor and blocks its ability to interact with hyaluronate. In the first set of experiments, we investigated the spontaneous aggregation of SV-3T3 cells, which involves two distinct mechanisms, one of which is dependent upon the presence of divalent cation and the other is independent. The divalent cation-independent aggregation was found to be completely inhibited by both intact and Fab fragments of the K-3 MAb. In contrast, the K-3 MAb had no effect on the divalent cation-dependent aggregation of cells. In a second set of experiments, we examined alveolar macrophages. The presence of hyaluronate receptors on alveolar macrophages was demonstrated by the fact that detergent extracts of these cells could bind [3H]hyaluronate, and this binding was blocked by the K-3 MAb. Immunoblot analysis of alveolar macrophages showed that the hyaluronate receptor had a Mr of 99,500, which is considerably larger than the 85,000 Mr for that on BHK cells. When hyaluronate was added to suspensions of alveolar macrophages, the cells were induced to aggregate. This effect was inhibited by the K-3 MAb, suggesting that the hyaluronate-induced aggregation was mediated by the receptor.

Animals↗

PubMed1988

Distribution of hyaluronate and hyaluronate receptors in the adult lung.

In the present study, we have examined the distribution of both hyaluronate receptors and hyaluronate in adult hamster lung. The receptor for hyaluronate is a transmembrane glycoprotein of Mr 85,000 that interacts with actin filaments and is thought to mediate many of the effects that hyaluronate has on cell behaviour, such as cell-to-cell adhesion and migration. It was localized histochemically with a monoclonal antibody, designated as K-3, which specifically binds to the receptor. Hyaluronate was detected by a biotinylated form of cartilage proteoglycan, which binds with high affinity and specificity to hyaluronate. At the light-microscopic level, both hyaluronate and its receptor were present on the basolateral surfaces of bronchial and bronchiolar epithelium, suggesting that these two components interact with each other. This interaction may be important for maintaining the attachment of the epithelium to the basement membrane. In addition, hyaluronate was present in the adventitial regions of large pulmonary blood vessels. Receptors for hyaluronate were also evident on the surfaces of pulmonary macrophages, as demonstrated by the fact that K-3 immunoreactive cells coincided with cells positive for non-specific esterase, a characteristic feature of macrophages. The receptors on pulmonary macrophages probably mediate the effects that hyaluronate has on these cells with respect to cell-to-cell adhesion and migration.

Animals↗