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Biomedical subjects

H N Claman

Publications and source records attributed to H N Claman.

At least 37 records · Page 2Linked to original sources
PubMed1990

Mast cells and fibrosis. The relevance to scleroderma.

Mast cells are being recognized as important constituents in fibrotic processes. This article reviews the evidence for increased mast cell numbers and/or function in a variety of fibrotic conditions. Increased mast cell numbers and activity are seen in chronic murine graft-versus-host disease (a model for scleroderma) and in active scleroderma itself. An integrated schema for scleroderma is presented, emphasizing the interactions among mast cells, endothelial cells, and fibroblasts mediated by heparin and heparin-binding growth factors.

Animals↗
PubMed1989

On scleroderma. Mast cells, endothelial cells, and fibroblasts.

An integrated view of the pathogenesis of scleroderma should include vascular, immunologic, and fibrotic processes. This review introduces the mast cell into this picture, emphasizing recent knowledge gained from a study of experimental chronic graft-vs-host disease and scleroderma itself. In both of these situations, increased mast cell activity occurs. A link between the activation of both endothelial cells and fibroblasts may be provided by the family of heparin-binding growth factors. These cytokines are produced by many cells and are bound, protected, and enhanced by heparin, which may be provided by the activated mast cells. These and other growth factors may be responsible for endothelial proliferation and excess collagen production by fibroblasts. This enlarged schema should provide additional points for therapeutic intervention in scleroderma.

Cell Differentiation↗
PubMed1989

Hepatic homing of mononuclear inflammatory cells isolated during murine chronic graft-vs-host disease.

Liver injury in murine chronic graft-vs-host disease (CGVHD) to minor histocompatibility Ag, B10.D2----BALB/c (600 rad), is characterized by mononuclear cell inflammation and necrosis of interlobular bile ducts. Bile duct destruction in this model is similar to that which occurs in human CGVHD, late liver transplant rejection, and primary biliary cirrhosis. This model provides a unique opportunity to isolate mononuclear inflammatory cells from the liver during CGVHD, study their functions, and investigate the immunologic mechanisms responsible for bile duct destruction. In the present study, we compared the in vivo organ homing of mononuclear inflammatory cells (MC) isolated from the liver and spleen during the course of CGVHD. MC isolated from the liver showed a progressive increase in homing to the livers of BALB/c mice from day 7 through 42. In contrast, the hepatic homing of MC isolated from the spleen peaked at day 21 and subsequently declined. CGVHD spleen MC showed a progressive increase in homing to the spleen of BALB/c mice whereas CGVHD liver MC showed no change over time. Homing to other organs was negligible. The hepatic and splenic homing of MC isolated during CGVHD was significantly greater in BALB/c (host) mice than in B10.D2 (donor) mice. Autoradiography was used to determine the intrahepatic sites at which CGVHD liver MC accumulate after i.v. injection into BALB/c mice. The results indicated that MC isolated from the liver when bile duct inflammation is most intense accumulate preferentially in hepatic portal spaces in close proximity to interlobular bile ducts. These results suggest that hepatic homing by CGVHD liver MC is specific for minor histocompatibility Ag expressed on host biliary epithelial cells. These data support the hypothesis that bile duct destruction in murine CGVHD is mediated by MC that are sensitized to minor histocompatibility Ag expressed by host biliary epithelial cells.

Animals↗
PubMed1989

Murine natural suppressor cells in the newborn, in bone marrow, and after cyclophosphamide. Genetic variations and dependence on IFN-gamma.

Natural suppressor (NS) cells are potent, Ag nonspecific, MHC-unrestricted inhibitors of immune responses. Murine NS activity is found in several situations, including adult bone marrow (BM) and neonatal/newborn spleen, and spleen following total lymphoid irradiation, after BM transplantation and after cyclophosphamide (CY) treatment. Using three of these situations (adult BM, newborn spleen, and spleen after CY treatment), the strain distribution of NS cell activity was assessed. A wide variation in potency is seen in both naturally occurring (adult BM and newborn spleen) and induced (after CY treatment) NS cell activity. Up to 10-fold differences in NS activity are seen between high and low NS strains. This reflects an intrinsic genetic variation between mouse strains in both naturally occurring and CY-induced NS cell activity. Thus, a strain with high NS activity at birth, has high NS activity in its BM as an adult and in its spleen after CY treatment. Of the strains tested, B10.D2 has the highest NS cell activity while BALB/c has the lowest, and the F1 between these two strains is intermediate in NS activity. Finally, the NS cell activity from all strains tested required IFN-gamma for expression of its inhibitory activity.

Aging↗
PubMed1989

Mast cell changes in a case of rapidly progressive scleroderma-ultrastructural analysis.

A 63-year-old woman had rapidly progressive scleroderma and died 4 months after the clinical appearance of her illness. Extreme itching of the affected skin was prominent. Electron microscopic study of the clinically uninvolved skin showed mainly normal mast cells. Mast cells in clinically involved skin showed a wide morphologic spectrum including evidence of cellular activation. There was an increased amount of cytoplasm occupied by polysomes and mitochondria and less cytoplasm occupied by granules. Most granules were pale and swollen, suggesting active degranulation. In some cases it was difficult to distinguish a hyperactive mast cell with only a few granules remaining from a fibroblast which had acquired granules by transgranulation. This case illustrates the active participation of mast cells in acute scleroderma.

Biopsy↗
PubMed1989

Ultrastructural evidence for mast cell activation in a case of neurofibromatosis.

Neurofibromas contain fibroblasts and many mast cells, and recent hypotheses have linked fibrous tissue growth to activated mast cells. We describe the ultrastructure of mast cells and fibroblasts in a case of neurofibromatosis. Mast cells were numerous and showed extensive signs of activation. Mast cells were often intimately associated with fibroblasts, and mast cell granules could be seen inside fibroblasts ('transgranulation'). The fibroblasts were also activated. These results suggest that interactions between mast cells and fibroblasts may be important in the prominent collagen production that takes place in these tumors.

Adult↗
PubMed1988

Suppression of cytotoxic T-cell generation by natural suppressor cells from mice with GVHD is partially reversed by indomethacin.

Natural suppressor cells from the spleens of mice with graft-versus-host disease produced across minor histocompatibility barriers inhibit the in vitro generation of alloreactive cytotoxic T lymphocytes by spleen cells from normal mice. The mechanism of natural suppression was studied; suppression does not require direct cell contact with targets. Exogenous interleukin-2 has no effect in reversing suppression while indomethacin partially reverses the suppression mediated by natural suppressor cells.

Animals↗
PubMed1988

Immunologic dysfunction in scleroderma: evidence for increased mast cell releasability and HLA-DR positivity in the dermis.

To investigate the role of mast cells and cell-mediated immunity in the pathogenesis of scleroderma, we studied wheal size after skin testing with compound 48/80, a liberator of mast cell histamine, and demonstrated increased mast cell releasability in skin that appeared normal, adjacent to involved skin. Immunofluorescent staining for HLA-DR showed dermal positivity in 12 of 13 involved- and 9 of 13 uninvolved-skin biopsy specimens from scleroderma patients, compared with only 1 of 10 controls. By immunoperoxidase staining, most of the DR positivity was found in fibroblast-like cells. These findings further support the notion of immunologic dysfunction in scleroderma.

Adolescent↗
PubMed1988

Evidence that IFN-gamma is responsible for natural suppressor activity in GVHD spleen and normal bone marrow.

Natural suppressor (NS) cells are capable of suppressing immunological responses in a nonspecific manner. Previously, we have described NS cells in the spleens of mice undergoing chronic graft-versus-host disease (GVHD) and also in normal B10.D2 bone marrow (BM). NS cells obtained from these environments appear dependent upon lymphokines for their ability to manifest suppression. In this report, with anti-IFN-gamma antibody, we show that IFN-gamma is necessary for NS cell activation. Anti-IFN-gamma antibody is able to remove the ability of NS cells to suppress a concanavalin A (Con A) proliferation assay. Also, anti-IFN-gamma antibody removes the ability of rIL-2, lectin-free Con A supernate (CAS), and recombinant IFN-gamma (rIFN-gamma) to enhance NS suppression of lipopolysaccharide response. By these criteria, IFN-gamma is required for NS cell activation, and rIL-2 may act indirectly by its ability to stimulate IFN-gamma synthesis. These results are discussed in the context of the immuno-suppression seen in human BM transplantation.

Animals↗
PubMed1988

Mast cells and neurofibromatosis.

Mast cells are in close contact with other cells in neurofibromatosis, e.g. neural cells and fibroblasts. Secretory products of mast cells may be important in the regulation of collagen synthesis by fibroblasts and Schwann cells. Newer methods of detecting mast cells by avidin staining of granules and localization of membrane Fc receptors for IgE have been exploited in at least one experimental model of fibrosis (murine chronic graft-versus-host disease). Such approaches should help in understanding parameters involved in modulation of cell growth in neurofibromas. Future directions for the study of cellular dynamics in neurofibromas should include detection of activated (degranulated) mast cells, Schwann cells and effects of mast cell products on collagen gene expression.

Fibrosis↗