Biomedical subjects

S Goerdt

Publications and source records attributed to S Goerdt.

107 records · Page 6Linked to original sources

PubMed1993

Immunohistochemical comparison of cutaneous histiocytoses and related skin disorders: diagnostic and histogenetic relevance of MS-1 high molecular weight protein expression.

Twenty-nine cases of Langerhans cell histiocytosis (LCH), non-Langerhans cell histiocytoses (N-LCH), non-infectious granulomas, and fibroblast-related lesions were examined with a panel of monoclonal and polyclonal antibodies on freshly frozen tissue sections to characterize the macrophage phenotype of N-LCH syndromes. MS-1 high molecular weight extracellular protein, specific for sinusoidal endothelial cells and dendritic perivascular macrophages in normal human organs, was expressed by N-LCH cells but was not found in LCH cells, epithelioid cells in sarcoidosis, or palisading histiocytes in granuloma annulare. The subcellular location of MS-1 protein, i.e., cytoplasmic vs. peripheral/extracellular, allowed discrimination of small and large (foamy or multinucleated) N-LCH cells. MS-1-positive cells, which were found intermingled in cellular dermatofibromas but not in fibrous dermatofibromas, differed from MS-1-positive N-LCH cells by their dendritic morphology, and thus rather resembled their normal dermal counterparts. A preserved functional relationship of these two MS-1-positive cell types was indicated by the fact that N-LCH and cellular dermatofibromas were the only lesions found to be highly vascularized. As expected, CD1a showed high specificity for LCH, while CD34 was predominantly expressed by fibroblast-related lesions; in cellular dermatofibromas, CD34 and MS-1 expression partially overlapped. The other antigens tested showed non-specific or overlapping patterns of expression. In conclusion, assessment of MS-1 protein expression (in addition to assessment of CD1a and CD34) promises to be of diagnostic value in the discrimination of N-LCH from related skin disorders, and it may indicate a common differentiative pathway for most N-LCH disease entities.

Antibodies, Monoclonal↗

PubMed1993

Nickel chloride and cobalt chloride, two common contact sensitizers, directly induce expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule (ELAM-1) by endothelial cells.

Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (ELAM-1, E-selectin) are endothelial surface molecules that play a role for leukocyte recruitment to sites of inflammation, e.g., during contact hypersensitivity. We studied the effects of sensitizing agents (2,4-dinitro-benzenesulfonic acid, metal salt haptens) and chemically related substances on endothelial adhesion molecule expression. Using flow cytometry and an enzyme-linked immunosorbent assay, NiCl2 and, to a lesser extent, CoCl2 were found to up-regulate ICAM-1, VCAM-1, and ELAM-1 expression on cultured human umbilical vein endothelium whereas the other substances tested showed no effects. Induction of adhesion molecules by NiCl2 required de novo mRNA and protein synthesis. Up-regulation could be blocked by kinase inhibitor H-7 but not staurosporine, suggesting involvement of phosphorylation events independent of protein kinase C activation. Concomitant application of NiCl2 and neutralizing antibodies to IL-1 did not block up-regulation by the hapten demonstrating that the latter did not act via an IL-1-dependent autocrine mechanism. Regarding ELAM-1 induction, pre-treatment for 24 h with NiCl2 produced hyporesponsiveness to IL-1 and TNF-alpha upon restimulation, suggesting that NiCl2 and these cytokines may partially share a common pathway of activation. In addition, analysis of cultured foreskin specimens revealed that NiCl2 may induce up-regulation of ELAM-1 on microvascular endothelium in vivo. Our data demonstrate that both Ni++ and Co++ to which simultaneous contact sensitivity is frequently observed have the ability to directly up-regulate endothelial adhesion molecules. This shared property may represent an adjuvant mechanism that promotes sensitization and elicitation events in contact hypersensitivity to these haptens.

Capillaries↗

PubMed1993

Carcinoembryonic antigen and related glycoproteins in psoriasis.

Psoriasis is a benign but hyperproliferative skin disease. Psoriatic basal cells show a phenotype similar to that of normal skin, while psoriatic suprabasal cells exhibit a qualitatively altered keratinization pathway, resulting in the absence of the granular layer. These cells further show an abnormal expression of cellular differentiation antigens, which does not lead to tumor development. This immunohistological study demonstrates the appearance of carcinoembryonic antigen (CEA) in psoriatic suprabasal cells below the parakeratotic layer, while other markers such as CEA-related antigens, the nonspecific cross-reacting antigens and alpha-fetoprotein are not expressed. CEA is absent in normal skin, lichen planus, ichthyosis vulgaris and allergic dermatitis. Our data support the notion that dedifferentiation of psoriatic suprabasal keratinocytes is due to the reactivation of early developmental patterns of differentiation in this disease.

Antibodies, Monoclonal↗

PubMed1993

Monoclonal antibody MS-44B reacts with human dendritic, glial and endothelial cells: differential expression of MS-44B antigen by epidermal dendritic cells and by MS-1+ splenic sinusoidal endothelial cells. An immunohistological study.

Rat monoclonal antibody MS-44B was raised against the dendritic human melanoma cell line SK-Mel 25 and detects highly dendritic cells and endothelial cells in various human organs. Among the cells recognized are dendritic cells in lymphoid organs, such as lymph node, tonsil and spleen, dendritic cells in skin, lung and lamina propria, (astro-)glial cells in the central nervous system and mesangial cells in the kidney. In peripheral lymph nodes (and less consistently in visceral lymph nodes), MS-44B reactive cells are found predominantly in the paracortical area and in the region of the marginal sinus; in tonsils these dendritic cells are concentrated at the outer rim of the follicle, while their distribution in the white pulp of the spleen is less well defined. In skin, both dermal and epidermal dendritic cells are stained. In the dermis just beneath the dermal-epidermal border, dendritic cells may be found with their processes protruding into the epidermal basal layer. MS-44B reactive epidermal dendritic cells send their processes in a horizontal direction or into the upper epidermal cell layers. MS-44B reactive epidermal dendritic cells are neither Langerhans cells, since they lack HLA-DR antigens and CD1, nor Merkel cells, since they lack cytokeratin expression. They rather seem to constitute a subpopulation of epidermal melanocytes that are low in tyrosinase expression and do not populate the melanocyte area of the hair bulb. With regard to the endothelium, monoclonal antibody MS-44B reveals marked heterogeneity in that it preferentially stains the endothelium of large and medium-sized arterial vessels, while capillary and venous endothelia are less well stained.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Changes in phenotypically distinct phagocyte subpopulations during nonspecific modulation of contact sensitization.

Environmental influences are increasingly recognized as nonspecific modulators triggering and aggravating allergic diseases. To obtain better insight into the pathomechanisms of these nonantigen-specific phenomena, we studied the augmenting and inhibitory effects of croton oil and glucocorticosteroid (GC) on the induction of murine allergic contact dermatitis. Application of the irritant croton oil simultaneously with the sensitization dose of the contact allergen oxazolone strongly amplified the inflammatory reaction (measured as ear swelling) during the effector phase. Immunohistologically, this effect correlated with an increased percentage of MRP8- and MRP14-positive phagocytes in the infiltrate of the early inflammatory reaction 8 h after sensitization with oxazolone plus croton oil as compared to oxazolone alone (62 vs. 27%; p < 0.05). Intravenously administered GC was used as an inhibitor of contact sensitization. The suppressive effect of GC on sensitization was dependent on the time of its application: suppression of the inflammatory reaction during the effector phase was clearly more pronounced when GC had been injected 1 day as compared to 1 h before sensitization. Correspondingly, the percentage of BM8-positive macrophages in the infiltrate of the early inflammatory reaction 8 h after sensitization was differentially decreased depending on the time of GC application: suppression of the percentage of BM8-positive macrophages was clearly more pronounced when GC had been injected 1 day as compared to 1 h before sensitization (17 vs. 25%; base value without GC 35%; p < 0.05). Furthermore, the percentage of BM8-positive macrophages in the inflammatory infiltrate of the effector phase was increased when sensitization had been enhanced by concomitant irritant contact dermatitis (47 vs. 59%; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Inducible expression of MS-1 high-molecular-weight protein by endothelial cells of continuous origin and by dendritic cells/macrophages in vivo and in vitro.

Recently, we have described a monoclonal antibody, named MS-1, which identifies a novel high-molecular-weight protein expressed by noncontinuous, sinusoidal endothelia and by interstitial dendritic cells in certain normal human organs (S Goerdt, LJ Walsh, GF Murphy, JS Pober, J Cell Biol 1991, 113:1425-1437; and LJ Walsh, S Goerdt, JS Pober, H Sueki, GF Murphy, Lab Invest 1991, 65: 732-741). In this report, we demonstrate in studying a variety of skin lesions that MS-1 antigen can also be expressed by endothelia of continuous origin under certain pathological conditions. Among the skin lesions tested, MS-1 antigen expression by endothelial cells of continuous origin is frequently observed in wound healing tissue, in cutaneous T-cell lymphoma, in psoriasis, and in melanoma metastasis, ie, in 100%, 80%, 71%, and 71% of cases, respectively. In contrast, endothelial MS-1 antigen expression rarely occurred in other skin lesions, including vascular tumors, six of which were Kaposi's sarcomas (13% and 0% of cases with vascular MS-1 expression, respectively). The percentage of cases with MS-1+ vessels is only marginally different in malignant versus benign lesions (55% versus 31%); when melanocytic nevi, primary melanomas, and melanoma metastases are compared, however, an increase in the percentage of cases with MS-1+ vessels is seen (31%, 50%, and 71%, respectively). Apart from wound healing, the relative number of MS-1+ vessels in a given lesion amounts to less than 5% compared with the number of continuous type vessels stained by monoclonal antibody 1F10 (S Goerdt, F Steckel, K Schulze-Osthoff, H-H Hagemeier, E Macher, C Sorg, Exp Cell Biol 1989, 57: 185-192). In addition, the occurrence of MS-1+ vessels is not related to the overall vascularity of a given lesion. Thus, the conditions for MS-1 antigen expression by endothelia of continuous origin cannot as yet be exactly defined. Furthermore, we have noticed that the number of MS-1+ dendritic cells varies considerably in skin lesions; in the early patch lesions of Kaposi's sarcoma and in juvenile xanthogranuloma MS-1+ cells even constitute the major cell type. This prompted us to investigate MS-1 antigen expression and its regulation in cultured human monocytes/macrophages. Expression of MS-1 antigen by these cells regularly starts at day 3 of culture and reaches its maximal value at day 9, after which it declines.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗

PubMed1992

Endothelial heterogeneity and the acquired immunodeficiency syndrome: a paradigm for the pathogenesis of vascular disorders.

Vascular disorders comprise a wide range of diverse disease entities. Correspondingly, vessels, and even more so the endothelial which line them, show a remarkable extent of heterogeneous differentiation, e.g. between the blood vascular and lymphatic systems, along the length of the vascular trees, and in the microvascular beds of various organs. The most important morphologic criterion to discriminate between endothelia is continuity (continuous endothelial cell layer and well-formed basement membrane) versus discontinuity (intra- or intercellular gaps and/or reduced or missing basement membrane). Most blood vascular endothelia are of the continuous type, while most sinusoidal and lymphatic endothelia are discontinuous by these criteria. Antigen expression corroborates these morphologic data in that CD31, CD34, and 1F10 antigen are exclusively expressed in continuous endothelia, while MS-1 antigen is preferentially expressed in non-continuous sinusoidal endothelia. In contrast, no specific marker has as yet been described for lymphatic endothelia. Endothelial heterogeneity substantially contributes to the pathogenesis of vascular disorders. For example, in patients with acquired immunodeficiency syndrome the same infectious agent may cause either bacillary angiomatosis (a lobular capillary proliferation) or peliosis (sinusoidal dilatation, endothelial denudation, and development of blood-filled cysts) depending on whether the affected organs have predominantly continuous endothelia or noncontinuous sinusoidal endothelia. Moreover, in Kaposi's sarcoma, it is still an open question of whether the lesion is derived from blood vascular or lymphatic endothelia (Kaposi's sarcoma cells in situ do not express the von Willebrand factor+, PAL-E+, 1F10+ phenotype of mature, resting blood vascular endothelia). It is also unresolved how endothelia of either type may be differentially induced to dedifferentiate and how they are recruited into the lesion. Clearly, knowledge about endothelial heterogeneity is still too incomplete to identify the actual mechanisms and molecules that govern the pathogenesis of vascular disorders (including still others than those mentioned here such as atherosclerosis, diabetic angiopathy, and rheumatoid arthritis) affecting distinct endothelia. Further efforts in antigenic phenotyping and in cell and molecular biology of heterogeneously differentiated endothelia should be made to improve this state of affairs.

Angiomatosis, Bacillary↗

PubMed1992

Monoclonal antibody H3/5-47 recognizes an inducible cell surface antigen expressed differently in endothelium of normal and diseased tissues and in vitro.

Monoclonal antibody H3/5-47 was raised against a human melanoma metastasis and recognizes an antigen expressed in the endothelial cells of all normal human organs as assessed by immunohistochemistry. Antigen expression is higher in venous than in capillary or arterial endothelia; capillary endothelia of different microvascular beds, such as skin, lung, gut or liver, may express varying amounts of this antigen. H3/5-47 antigen expression in the endothelia of diseased tissues (inflammatory diseases, neoplasias) largely reflects its expression pattern in normal tissues. As might be anticipated, the highest expression of H3/5-47 antigen is found in resting adult cutaneous and hepatic cavernous venous hemangiomas. In contrast, psoriatic vessels, characterized by hypertrophy and fenestrations, tend to express H3/5-47 antigen at a much lower density. In human umbilical vein endothelial cells, half the single donor cases show no expression of H3/5-47 antigen, while the rest express the antigen at relatively low densities in about half the cells. Treatment with interferon-gamma or thrombin, but not interleukin-1, lipopolysaccharide, endothelial cell growth factor or phorbolester, either enhances or induces de novo expression in cultured human umbilical vein endothelial cells within 24h; maximum expression of H3/5-47 antigen is induced by interferon-gamma within 72 h. H3/5-47 antigen is not similar to other antigens inducible in human umbilical vein endothelial cells such as HLA-DR, ICAM-1, HECA-452, Leu13, MCP-1 or gamma-IP-10. It is not specifically expressed in the endothelium as it may also recognize certain epithelia, peripheral nervous tissue and bone marrow-derived cell populations.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

PubMed1991

Identification of a novel high molecular weight protein preferentially expressed by sinusoidal endothelial cells in normal human tissues.

Mouse mAb MS-1, raised against human spleen, detects an endothelial cell antigen abundantly expressed by the sinusoidal endothelia of spleen, lymph node, liver, and adrenal cortex, but absent from nonsinusoidal continuous endothelia in these organs. Immunoelectron microscopy of splenic tissue demonstrates that the MS-1 antigen is predominantly deposited at zones of intercellular contact between adjacent sinusoidal endothelial cells. mAb MS-1 also reacts with a variable proportion of high endothelial venules in tonsil, but not in other lymphoid tissues, and with an interstitial dendritic cell population most abundant in placenta. mAb MS-1 does not react with cultured resting or mediator- activated human umbilical vein endothelial cells, dermal fibroblasts, peripheral blood mononuclear cells, or the cell lines U937, HL-60, K562 or Mo7E; it does react with the primitive myeloid cell line KG-1. mAb MS-1 immunoprecipitates a major protein of 215 kD and minor proteins of 320 and 120 kD from splenic extracts as analyzed by SDS-PAGE with reduction. These proteins are soluble in aqueous buffers. Immunoprecipitation from KG-1 cell lysates detects four proteins of 280, 300, 205, and 120 kD; the 300-, 205-, and 120-kD species, presumably corresponding to the 320-, 215-, and 120-kD species in spleen, respectively, are secreted into the media. Under nonreducing conditions, immunoprecipitates from KG-1 cell lysates or conditioned media contain one predominant 300-kD species; upon isolation and reduction, this 300-kD species separates into the previously observed 300-, 205-, and 120-kD species. Pulse-chase experiments and limited proteolysis peptide mapping suggest that the 280-kD species is a precursor of the mature 300-kD species which may be subsequently cleaved to yield the 205- and 120-kD species. Because of its size, solubility and expression pattern, the antigen recognized by mAb MS-1 is likely to be an extracellular matrix protein utilized by endothelial cells of contorted, large caliber, or leaky microvessels that lack a well-formed basement membrane.

Adrenal Cortex↗

PubMed1991

MS-1 sinusoidal endothelial antigen is expressed by factor XIIIa+, HLA-DR+ dermal perivascular dendritic cells.

We have recently described a monoclonal antibody, termed MS-1, which reacts with sinusoidal endothelium as well as interstitial cells in a variety of nonlymphoid organs. In this report, we characterize the phenotypes of MS-1-positive cells in normal human skin. Double immunohistochemical and immunofluorescence labeling techniques demonstrate that MS-1 antibody identifies two cell types in human dermis: the first represented by weakly reactive lymphatic endothelial cells; and the second comprised of strongly reactive, highly dendritic perivascular cells which constitutively express both HLA-DR and factor XIIIa. These MS-1-positive dendritic interstitial cells are ultrastructurally distinctive, separate from mast cells, phagocytic macrophages, pericytes, blood vascular endothelial cells, and fibroblasts. MS-1-positive cells express this protein in discrete cytoplasmic compartments, and possibly as small plasma membrane-associated regions. The phenotype, dendritic morphology, and perivascular localization of MS-1-positive cells suggest that MS-1 antibody recognizes an epitope expressed by cells previously referred to as dermal perivascular dendritic cells or dermal dendrocytes. We have proposed that MS-1 protein may serve as an anchoring molecule for endothelial cells in sinusoidal spaces in the absence of well-formed basement membranes. MS-1 may similarly function to maintain the spatial relationship of dermal perivascular dendritic cells with the microvasculature.

Antigen-Presenting Cells↗

PubMed1990

Expression of basic fibroblast growth factor (bFGF) in Kaposi's sarcoma: an immunohistologic study.

Ten cases of Kaposi's sarcoma (KS) including five AIDS-KS, one classical KS, and four pseudo-KS (acroangiodermatitis) were investigated for their expression of basic fibroblast growth factor. Antigen expression was demonstrated by immunoperoxidase staining of cryostat sections with affinity-purified anti-bFGF antibodies. It was found that bFGF was strongly expressed in basal and suprabasal keratinocytes, which were also intensively stained in normal skin biopsies. The growth factor was generally absent from the endothelial cells and spindle cells of the neoplasms. These cell types exhibited a very faint staining in a small number of lesions. The studies provide strong evidence that proliferation of KS tumor cells may not be explained by autocrine secretion mechanism of the growth factor, which has been suggested in previous reports with in vitro cultured KS cell lines.

Acquired Immunodeficiency Syndrome↗

PubMed1989

Characterization and differential expression of an endothelial cell-specific surface antigen in continuous and sinusoidal endothelial, in skin vascular lesions and in vitro.

Continuous and sinusoidal endothelial cells display marked morphological and functional heterogeneity as to their plasmalemmal vesicle content, to the kind of intercellular junctional complexes, to the existence and kind of fenestrae and gaps, to the existence and character of their basement membrane, to their ability for phagocytosis and to other functional parameters. Monoclonal antibody 1F10, raised against human umbilical vein endothelial cells (HUVE cells), reflects these differences in recognizing--without any nonendothelial side reactions--an endothelial cell surface antigen, abundantly expressed in continuous endothelia, low and inconsistently expressed in liver sinusoidal and dermal lymphatic endothelia and absent from splenic sinusoidal endothelial cells. In differentiated skin vascular tumors, 1F10 antigen is expressed in normal amounts while it is only low and inconsistently expressed in the dedifferentiated endothelial cells of Kaposi's sarcoma and hemangiosarcoma. HUVE cells in culture, in contrast to their in situ ancestors, express variable amounts of 1F10 antigen. When endothelial cell-conditioned medium (ECC medium) is supplied to HUVE cells in culture, no 1F10 antigen is expressed, while supplementation with fresh serum-containing medium (FSC medium) or cytokines, such as bFGF, suffices to maintain 1F10 expression in 10-70% of the cells. From this we conclude that developmental regulation, environmental influences and cytokine supply contribute to the differentiation and maintenance of the 1F10+ and 1F10-endothelial cell phenotypes, both in vivo and in vitro.

Animals↗

PubMed1987

Characterization and expression kinetics of an endothelial cell activation antigen present in vivo only in acute inflammatory tissues.

Endothelial cell activation by endotoxin (LPS), tumor necrosis factor (TNF), Interleukin-1-alpha, beta (IL-1-alpha, beta) and phorbolesters (TPA) results in increased monocyte adhesion. Examination of kinetics of monocyte adhesion shows that the onset of adherence enhancement (AE) is similar in all five agents (about 300% AE at 6 h), while its decrease is delayed in LPS/TNF versus IL-1-alpha, beta/TPA-induced activation (LPS versus IL-1-beta:260% versus 60% at 18 h). Monoclonal antibody (4D10), raised against 24 h LPS-stimulated endothelial cells detects an endothelial cell-specific activation antigen at Mr 81,000 that is induced by LPS, TNF, IL-1-alpha, beta and TPA (within 6 h about 100% positive cells). Decrease in antigen-positive cells is delayed in LPS/TNF versus IL-1-alpha, beta/TPA-induced antigen expression (LPS vs. IL-1-beta: 60% vs. 5% at 24 h). In situ the antigen is not expressed in normal and chronic inflammatory tissues. Acute inflammatory tissues, including contact and atopic dermatitis, psoriasis and periodontitis, however, show endothelial cells staining strongly positive. In contact eczemas at different times after elicitation (0, 6, 24, 72, 96 h), expression of the antigen is first seen after 24 h and is still strong at 96 h. These data indicate that LPS/TNF conduct an endothelial cell activation program in vitro, showing the same prolonged kinetics that is found for endothelial cell activation in the acute inflammatory process in vivo.

Antibodies, Monoclonal↗

PubMed1986

A monoclonal antibody reacting with endothelial cells of budding vessels in tumors and inflammatory tissues, and non-reactive with normal adult tissues.

This report describes a monoclonal antibody (MAb) generated by immunization of mice with cell suspensions of capillary-rich fragments of mammary carcinomas. The antibody (EN 7/44) belongs to the IgM class and detects a 30.5 kDa antigen which is found in the cytoplasm of human placental and umbilical vein-endothelial cells (HUVEC) and on the surface of tumor endothelium. Using indirect immunofluorescence and immunoperoxidase techniques, we did not find the MAb in peripheral blood cells or in any human cell lines tested, nor in endothelial cells from normal, nonproliferating adult tissues. Positively staining endothelium was found in the placenta, the umbilical vein and in proliferating normal tissues (intestine). Positive endothelial cells were found in acute inflammatory reactions and in tumors. In the latter, the strongest reactions were seen in newly formed budding capillaries, which were identified by their reactivity with Ulex europaeus I-lectin and antibodies against F VIII-RAG. In tumor tissues, large vessels could be positively stained with the EN 7/44 antigen, in contrast to inflammatory tissues. It is concluded that endothelial cells at the tip of a budding capillary express distinct phenotypic characteristics.

Adult↗

PubMedDate not supplied

Langerhans cells do not express alternative macrophage activation-associated CC chemokine (AMAC)-1.

We have cloned a novel human CC chemokine, alternative macrophage activation-associated CC chemokine (AMAC)-1 that is highly homologous to macrophage inflammatory protein (MIP)-1alpha. In contrast to MIP-1alpha, AMAC-1 is induced in macrophages by Th2-associated cytokines IL4, IL13, and IL10 in vitro; in addition, AMAC-1 is expressed by Th1-suppressive alveolar macrophages in vivo. Surprisingly, however, AMAC-1 is also expressed by GM-CSF-induced, in vitro monocyte-derived dendritic cells when treated by IL4. Here, we present a detailed analysis of AMAC-1 expression in monocyte-derived dendritic cells in vitro and show that the prime dendritic cells in vivo, i.e. epidermal Langerhans cells, do not express AMAC-1 mRNA. In conclusion, AMAC-1 is a novel CC chemokine whose Th2-associated expression pattern in alternatively activated suppressor macrophages in vivo and in vitro and its absence from epidermal Langerhans cells in vivo suggest that it may be involved in inhibition of Th1 reactions and in tolerance induction.

Chemokines, CC↗

PubMedDate not supplied

Stabilin-1, a homeostatic scavenger receptor with multiple functions.

The multifunctional scavenger receptor stabilin-1 (STAB1, FEEL-1, CLEVER-1, KIAA0246) was originally identified as the MS-1 antigen, expressed by sinusoidal endothelial cells in human spleen. Extensive histological studies revealed that stabilin-1 is also expressed by tissue macrophages and sinusoidal endothelial cells in the healthy organism; its expression on both macrophages and different subtypes of endothelial cells is induced during chronic inflammation and tumorigenesis. In vitro induction of stabilin-1 in macrophages requires the presence of glucocorticoids. Stabilin-1 is involved in two intracellular trafficking pathways: receptor mediated endocytosis and recycling; and shuttling between the endosomal compartment and trans-Golgi network (TGN). The latter intracellular pathway of stabilin-1 trafficking is mediated by GGAs, clathrin adaptors that interact with the DDSLL motif in the cytoplasmic tail of stabilin-1. When expressed by alternatively activated macrophages, stabilin-1 mediates the uptake and targeting for degradation of acLDL and SPARC, a regulator of tissue remodeling. Likewise, stabilin-1 in macrophages is involved in intracellular sorting and lysosomal delivery of the novel stabilin- 1-interacting chitinase-like protein (SI-CLP). Indirect evidence suggests that stabilin-1 is involved in adhesion and transmigration in various cell types (including tumor cells, leukocytes, and lymphocytes); however, its rapid recycling and scant level of surface expression argue against its universal role in cell adhesion. In summary, stabilin-1 is a homeostatic receptor which links signals from the extracellular environment to intracellular vesicular processes, creating a potential impact on the macrophage secretion profile.

Animals↗

PubMedDate not supplied

Alternatively activated antigen-presenting cells: molecular repertoire, immune regulation, and healing.

The Th1/Th2 paradigm has stimulated extensive research into the mechanisms underlying T-cell polarization; alternative activation of antigen-presenting cells (APCs) has turned out to be the corresponding concept APC polarization. Macrophages (M phi) as well as dendritic cells (DCs) can undergo Th1- or Th2-like polarization; APC1 and APC2 thus acquire the capacity to drive the development of naive T cells and the reactivation of resting T cells towards either a Th1 or a Th2 phenotype, respectively. Among polarized APC, effector macrophages are classically activated by mediators such as IFN-gamma, TNF-alpha or LPS (M phi 1), while M phi 2 are alternatively activated by IL-4, IL-10 or PGE(2). M phi 2 exhibit a unique molecular repertoire including receptors of innate immunity with broad specificity for foreign antigen and anti-inflammatory cytokines such as IL-1 receptor antagonist and alternative macrophage activation-associated CC-chemokine (AMAC)-1. While DC1 are well characterized, contradictory results have been obtained for DC2 that may either represent immature myeloid DCs or lymphoid DCs. Altogether, APC2 have come to age; they mediate Th2 differentiation, tolerance induction, downregulation of inflammation and healing. Thus, APC2 represent a hitherto neglected, but indispensable major pathway of APC activation and function.

Animals↗