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L M Stoolman

Publications and source records attributed to L M Stoolman.

At least 37 records · Page 2Linked to original sources
PubMed1993

Monocyte-endothelial adhesion in chronic rheumatoid arthritis. In situ detection of selectin and integrin-dependent interactions.

Blood monocytes are the principal reservoir for tissue macrophages in rheumatoid synovitis. Receptor-mediated adhesive interactions between circulating cells and the synovial venules initiate recruitment. These interactions have been studied primarily in cultured endothelial cells. Thus the functional activities of specific adhesion receptors, such as the endothelial selectins and the leukocytic integrins, have not been evaluated directly in diseased tissues. We therefore examined monocyte-microvascular interactions in rheumatoid synovitis by modifying the Stamper-Woodruff frozen section binding assay initially developed to study lymphocyte homing. Specific binding of monocytes to venules lined by low or high endothelium occurred at concentrations as low as 5 x 10(5) cells/ml. mAbs specific for P-selectin (CD62, GMP-140/PADGEM) blocked adhesion by > 90% in all synovitis specimens examined. In contrast, P-selectin-mediated adhesion to the microvasculature was either lower or absent in frozen sections of normal foreskin and placenta. mAbs specific for E-selectin (ELAM-1) blocked 20-50% of monocyte attachment in several RA synovial specimens but had no effect in others. mAbs specific for LFA-1, Mo1/Mac 1, the integrin beta 2-chain, and L-selectin individually inhibited 30-40% of adhesion. An mAb specific for the integrin beta 1-chain inhibited the attachment of elutriated monocytes up to 20%. We conclude that P-selectin associated with the synovial microvasculature initiates shear-resistant adhesion of monocytes in the Stamper-Woodruff assay and stabilizes bonds formed by other selectins and the integrins. Thus the frozen section binding assay permits direct evaluation of leukocyte-microvascular adhesive interactions in inflamed tissues and suggests a prominent role for P-selectin in monocyte recruitment in vivo.

Arthritis, Rheumatoid↗
PubMed1992

HUT 78 T cells bind to noncytokine-stimulated keratinocytes using a non-CD18-dependent adhesion pathway.

The initial in vitro observation that cultured keratinocytes, when treated with cytokines such as gamma interferon, increased the binding of T lymphocytes, opened up a whole new avenue of research to understand epidermal trafficking patterns in inflammatory skin diseases. A growing body of data strongly supports the in vivo role of lymphocyte-function-associated antigen-1 (CD18) expression by T cells in the binding to intercellular adhesion molecule-1 (CD54) expressing keratinocytes. To further explore the molecular basis for other possible adhesive interactions involving T cells and skin-derived cellular constituents, the authors used 2 cell lines (HUT 78 cells and Jurkat cells) and added them to multipassaged human keratinocytes, fibroblasts, and melanocytes. The skin-derived cells were treated with cytokines alone, or in combination, with a phorbol ester. HUT cells were capable of binding to keratinocytes in the absence of pretreatment with cytokines at 25 degrees C, which was not inhibited by anti-CD18 antibodies, or sensitive to reducing the temperature of the adhesion assay to 7 degrees C. Fibroblasts and melanocytes also constitutively bound HUT cells, but the binding to fibroblasts was highly temperature-sensitive. When keratinocytes were pretreated for 48 hours with gamma interferon plus phorbol ester, a "superadhesive" state was induced, resulting in a synergistically increased binding ability of both HUT cells and Jurkat cells. This effect was related to quantitative increases in keratinocyte intercellular adhesion molecule-1 expression. Several other clear-cut qualitative and quantitative differences were detectable in the ability of HUT cells and JS cells to bind to nontreated and cytokine/phorbol ester-treated keratinocytes, fibroblasts, and melanocytes. These results emphasize the complexity of molecular associations underlying T-cell trafficking patterns, potentially operative in the dermal and epidermal compartments of the skin.

Antigens, CD↗
PubMed1992

Adhesion molecules involved in the trafficking of normal and malignant leukocytes.

Adhesion molecules involved in leukocyte recruitment and lymphocyte recirculation impact on several aspects of tumor biology--the primary host response, the delivery of effective adoptive immunotherapy and the hematogenous spread of malignant cells. Common to all three processes are receptor-mediated adhesive interactions between circulating cells and the vessel wall. Recruitment of circulating lymphocytes, monocytes and natural killer cells is essential for an effective host response or successful adoptive immunotherapy. Thus poor induction or blockade of leukocyte binding sites on the microvasculature of tumor implants may help malignancies evade natural defenses. In addition, perturbation of adhesion receptor function during ex vivo expansion may alter the behavior of infused cells in adoptive immunotherapy protocols. Finally, circulating malignant cells may utilize receptors normally involved in recruitment and recirculation. This paper reviews the function and regulation of adhesion molecules involved in normal leukocyte trafficking. The evidence implicating specific adhesion receptors in the spread of lymphoid malignancies through the bloodstream is then discussed.

Animals↗
PubMed1991

Molecular mapping of functional domains of the leukocyte receptor for endothelium, LAM-1.

The human lymphocyte homing receptor LAM-1, like its murine counterpart MEL-14, functions as a mammalian lectin, and mediates the binding of leukocytes to specialized high endothelial cells in lymphoid organs (HEV). LAM-1 is a member of a new family of cell adhesion molecules, termed selectins or LEC-CAMs, which also includes ELAM-1 and PAD-GEM (GMP-140/CD62). To localize the regions of LAM-1 that are involved in cell adhesion, we developed chimeric selectins, in which various domains of PAD-GEM were substituted into LAM-1, and used these chimeric proteins to define the domain requirements for carbohydrate binding, and to localize the regions recognized by several mAb which inhibit the adhesion of lymphocytes to lymph node HEV. The binding of PPME or fucoidin, soluble complex carbohydrates that specifically define the lectin activity of LAM-1 and MEL-14, required only the lectin domain of LAM-1. The LAM1-1, LAM1-3, and LAM1-6 mAb each strongly inhibit the binding of lymphocytes to HEV in the in vitro frozen section assay, and defined three independent epitopes on LAM-1. Blocking of PPME or fucoidin binding by LAM1-3 indicated that this site is identical, or in close proximity, to the carbohydrate binding site, and analysis of the binding of LAM1-3 to chimeric selectins showed that the epitope detected by LAM1-3 is located within the lectin domain. Although the LAM1-6 epitope is also located in the lectin domain, LAM1-6 did not affect the binding of PPME or fucoidin. The LAM1-1 epitope was located in, or required, the EGF domain, and, importantly, binding of LAM1-1 significantly enhanced the binding of both PPME and fucoidin. These results suggest that adhesion mediated by LAM-1 may involve cooperativity between functionally and spatially distinct sites, and support previous data suggesting a role for the EGF domain of LAM-1 in lymphocyte adhesion to HEV.

Amino Acid Sequence↗
PubMed1990

CD11c (LEU-M5) expression characterizes a B-cell chronic lymphoproliferative disorder with features of both chronic lymphocytic leukemia and hairy cell leukemia.

Chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL) are two common chronic lymphoproliferative disorders, each having characteristic clinical, morphologic, and immunologic features. Phenotypically, CD5 reactivity in CLL and CD11c (Leu-M5) reactivity in HCL have characterized these two leukemias among B-cell disorders. In this study, we report 14 cases of a novel chronic lymphoproliferative disorder characterized by lymphocytosis and CD11c expression, but morphologically similar to CLL. The patients' ages ranged from 46 to 81 years (median 62). Eleven had palpable splenomegaly, five with markedly enlarged spleens; only one patient had generalized lymphadenopathy. The white blood cell count ranged from 5.2 to 131.0 x 10(9)/L (median 20.8). The morphologic diagnosis in all cases was CLL, with the cells usually having abundant cytoplasm. No morphologic features, of hairy cells were evident; tartrate-resistant acid phosphatase cytochemistry was negative in all cases. Bone marrow biopsies were available in 8 of 14. Four showed focal nodular infiltrates and two had diffuse infiltrates similar to CLL; two showed only minimal interstitial involvement. All cases expressed multiple B-cell markers, and 12 of 14 had monoclonal surface immunoglobulin. The leukemic cells of all cases strongly expressed CD11c, while CD5 was expressed in 7 of 14; only 1 of the 14 cases expressed the lymph node homing receptor, Leu-8. This unique group of leukemias appears to represent the malignant transformation of lymphocytes arising from a stage of lymphocyte differentiation between that found in typical cases of CLL and that of HCL. CD11c is known to have an important function in cellular adhesion and may be important in determining the pattern of lymphocyte tissue distribution found in this group of patients.

Acid Phosphatase↗
PubMed1990

ELAM-1--dependent cell adhesion to vascular endothelium determined by a transfected human fucosyltransferase cDNA.

Adhesion of circulating leukocytes to the vascular endothelium during inflammation is mediated in part by their interaction with the endothelial-leukocyte adhesion molecule ELAM-1. ELAM-1, a member of the LEC-CAM family of cell adhesion molecules, expresses an N-terminal carbohydrate recognition domain (CRD) homologous to various calcium-dependent mammalian lectins. However, the contribution of the CRD to cell adhesion and its carbohydrate binding specificity have not been elucidated. This study demonstrates that transfection of a human fucosyltransferase cDNA into nonmyeloid cell lines confers ELAM-1--dependent endothelial adhesion. Binding activity correlates with de novo cell surface expression of the sialylated Lewis x tetrasaccharide, whose biosynthesis is determined by the transfected fucosyltransferase cDNA. We propose that specific alpha(1,3)fucosyltransferases regulate cell adhesion to ELAM-1 by modulating cell surface expression of one or more alpha(2,3)sialylated, alpha(1,3)fucosylated lactosaminoglycans represented by the sialyl Lewis x carbohydrate determinant.

Animals↗
PubMed1990

Kappa light chain gene rearrangement in T-cell acute lymphoblastic leukemia.

Immunoglobulin and T-cell receptor gene rearrangement assays are sensitive methods of detecting clonality in lymphoproliferative disorders. The lack of lineage specificity of immunoglobulin heavy chain and T-cell receptor beta and gamma gene probes in acute leukemia is well established. However, immunoglobulin light chain gene rearrangement traditionally has been considered a highly specific indicator of a clonal B-lineage process. The authors describe a case of T-cell acute lymphoblastic leukemia in which Southern blot hybridization studies showed rearrangement of the T-cell receptor beta chain gene. Unexpectedly, the immunoglobulin kappa light chain gene also was rearranged; no immunoglobulin heavy chain gene rearrangement was seen. Kappa rearrangement was confirmed with the use of three restriction endonucleases. No rearrangements were seen from normal skin tissue, making a restriction enzyme site polymorphism highly unlikely. Northern blot studies showed a normal-size, T-cell receptor beta chain gene transcript; no immunoglobulin RNA was identified. These results describe the first reported case of kappa light chain gene rearrangement in a T-cell acute lymphoblastic leukemia. The findings emphasize the necessity of interpreting molecular hybridization studies in conjunction with routine morphology and immunophenotyping studies.

Aged↗
PubMed1990

Immunophenotypic aberrancy in adult acute lymphoblastic leukemia.

Some recent reports indicate a high frequency of immunophenotypic aberrancy in acute lymphoblastic leukemia (ALL). To investigate this issue with regard to adult ALL, the authors reviewed the immunophenotyping data from 39 cases analyzed in their clinical laboratory. Flow cytometric analysis of peripheral blood and/or bone marrow was performed with the use of a panel of 21 B-cell, T-cell, and myeloid monoclonal antibodies (MoAbs). The surface antigen profiles of the leukemic cells were compared with those of normal bone marrow and thymic counterparts, as defined by current models. Twenty-six cases were B-precursor ALL, 8 were T-ALL, and 3 were B-ALL (Burkitt's leukemia). Only two cases coexpressed lymphoid and myeloid antigens. In contrast, intralineage aberrancy was quite common. Immunophenotypes from 13 of 26 B-precursor ALL cases deviated from normal B-lineage marrow cells as defined by a recent classification. The T-ALL cases were also immunophenotypically heterogeneous. This high incidence of aberrant antigen expression in adult ALL suggests that leukemogenesis also involves aberrant differentiation rather than purely a process of maturational arrest.

Adolescent↗
PubMed1990

Identification of two related markers for common acute lymphoblastic leukemia as heat shock proteins.

By direct analysis of the polypeptide constituents of leukemic cells, we have previously detected several polypeptides that are restricted in their expression to acute lymphoblastic leukemia (ALL). In this study, we provide evidence that two polypeptides designated L2 and L4 are structurally related and represent novel markers for common ALL. Partial amino acid sequence analysis did not uncover differences between L2 and L4. The sequences obtained correspond to a previously cloned human gene designated hsp 27 that is expressed, following heat shock treatment, in a variety of cells. 32Pi incorporation studies indicate that L4 is an unphosphorylated form and L2 is a phosphorylated form of hsp27. The two forms were inducible by heat shock in leukemic and nonleukemic lymphoid cells. Thus, in acute leukemia, the common ALL subtype is uniquely characterized by the constitutive expression of a polypeptide that represents a major cellular phosphoprotein.

Amino Acid Sequence↗
PubMed1989

Adhesion molecules controlling lymphocyte migration.

Two newly characterized structural families of adhesion molecules, in concert with known members of the integrin and immunoglobulin supergene families, mediate the interaction of circulating lymphoid cells with the vessel wall. The Hermes/CD44 antigen family participates in attachment to multiple vascular beds and consists of a common polypeptide core showing amino-terminal homology to cartilage link proteins. In contrast, the node-specific homing receptor Mel-14 consists of substructures homologous to calcium-dependent lectins, EGF, and complement binding proteins. The sequence of Mel-14 provides structural support for the hypothesis that lectin-carbohydrate interactions mediate physiologically significant adhesion events in the course of lymphocyte recirculation. The discovery of a similar structure in ELAM-1 and GMP-140 extends the reach of this family to other leukocyte and platelet interactions with the vessel wall.

Animals↗
PubMed1989

Adhesion molecules of cultured hematopoietic malignancies. A calcium-dependent lectin is the principle mediator of binding to the high endothelial venule of lymph nodes.

This study documents that a calcium-dependent phosphomanosyl-binding site on human lymphoid malignancies mediates attachment to the peripheral node high endothelial venule (PNHEV). The phorbol ester PMA coordinately upregulates lectin activity and binding to the PNHEV in the human T-lymphoblastic cell line Jurkat but not in the less phenotypically mature lines HSB2, Molt4, CEM, and HPB-ALL. In contrast, expression of CD18, CD2, and several common epitopes of the putative adhesion receptor gp90Hermes (CD44) did not correlate with attachment to PNHEV in this series of cell lines. Insensitivity to inhibition by the CD18 MAb TS 1.18, temperature and divalent cation requirements further distinguish the Jurkat-PNHEV adhesive interaction from CD11a/18- and CD2-mediated adhesion. The PMA-induced phenotypic changes in the Jurkat line parallel late thymocyte differentiation as well as lymphocyte activation, suggesting that expression of the endothelial-binding lectin may be linked to one or both of these processes. The lectin-like activity on Jurkat cells is functionally indistinguishable from those previously linked to PNHEV recognition in normal human lymphocytes, normal rat lymphocytes and both normal and malignant murine lymphoid cells. In the mouse, this activity is either contained in or functionally linked to a member of the LEC-CAM family gp90Mel14, suggesting that Jurkat cells express the human homologue of the murine nodal homing receptor. Thus cultured T lymphoblastic malignancies express a variety of potential endothelial adhesion molecules but use primarily a highly conserved surface lectin to interact with PNHEV.

Animals↗
PubMed1987

Phosphomannosyl-derivatized beads detect a receptor involved in lymphocyte homing.

Recirculating lymphocytes initiate extravasation from the blood stream by binding to specialized high endothelial venules (HEV) within peripheral lymph nodes (PN) and other secondary lymphoid organs. We have previously reported that lymphocyte attachment to PN HEV is selectively inhibited by mannose-6-phosphate (M6P) and related carbohydrates (Stoolman, L. M., T. S. Tenforde, and S. D. Rosen, 1984, J. Cell Biol., 99:1535-1540). In the present study, we employ a novel cell-surface probe consisting of fluorescent beads derivatized with PPME, a M6P-rich polysaccharide. PPME beads directly identify a carbohydrate-binding receptor on the surface of mouse lymphocytes. In every way examined, lymphocyte attachment to PPME beads (measured by flow cytofluorometry) mimics the interaction of lymphocytes with PN HEV (measured in the Stamper-Woodruff in vitro assay): both interactions are selectively inhibited by the same panel of structurally related carbohydrates, are calcium-dependent, and are sensitive to mild treatment of the lymphocytes with trypsin. In addition, thymocytes and a thymic lymphoma, S49, bind poorly to PPME beads in correspondence to their weak ability to bind to HEV. When the S49 cell line was subjected to a selection procedure with PPME beads, the ability of the cells to bind PPME beads, as well as their ability to bind to PN HEV, increased six- to eightfold. We conclude that a carbohydrate-binding receptor on mouse lymphocytes, detected by PPME beads, is involved in lymphocyte attachment to PN HEV.

Animals↗
PubMed1987

Receptors involved in lymphocyte homing: relationship between a carbohydrate-binding receptor and the MEL-14 antigen.

Blood-borne lymphocytes extravasate in large numbers within peripheral lymph nodes (PN) and other secondary lymphoid organs. It has been proposed that the initiation of extravasation is based upon a family of cell adhesion molecules (homing receptors) that mediate lymphocyte attachment to specialized high endothelial venules (HEV) within the lymphoid tissues. A putative homing receptor has been identified by the monoclonal antibody, MEL-14, which recognizes an 80-90-kD glycoprotein on the surface of mouse lymphocytes and blocks the attachment of lymphocytes to PN HEV. In a companion study we characterize a carbohydrate-binding receptor on the surface of mouse lymphocytes that also appears to be involved in the interaction of lymphocytes with PN HEV. This receptor selectively binds to fluorescent beads derivatized with PPME, a polysaccharide rich in mannose-6-phosphate. In this report we examine the relationship between this carbohydrate-binding receptor and the putative homing receptor identified by the MEL-14 antibody. We found that: MEL-14 completely and selectively blocks the activity of the carbohydrate-binding receptor on mouse lymphocytes; the ability of six lymphoma cell lines to bind PPME beads correlates with cell-surface expression of the MEL-14 antigen, as well as PN HEV-binding activity; selection of lymphoma cell line variants for PPME-bead binding by fluorescence-activated cell sorting (FACS) produces highly correlated (r = 0.974, P less than 0.001) and selective changes in MEL-14 antigen expression. These results show that the carbohydrate-binding receptor on lymphocytes and the MEL-14 antigen, which have been independently implicated as receptors involved in PN-specific HEV attachment, are very closely related, if not identical, molecules.

Animals↗
PubMed1987

Homing receptors on human and rodent lymphocytes--evidence for a conserved carbohydrate-binding specificity.

Lymphocyte recirculation begins with the attachment of circulating cells to the structurally distinctive postcapillary venules of lymphoid organs termed high-endothelial venules (HEVs). In both rodents and humans, the attachment of lymphocytes to the HEVs of peripheral lymph nodes (PNs) on the one hand and gut-associated lymphoid tissues (GALTs) on the other appears to involve discrete adhesive structures on the surfaces of the interacting cells. In rodents, we previously showed that a carbohydrate-binding receptor at the lymphocyte surface participates in the attachment to the HEV of peripheral nodes. The studies reported herein document the involvement of a similar receptor in the selective attachment of human peripheral blood lymphocytes to the HEVs of PNs. We argue that the close functional relationship between the human and rodent receptors indicates that this component of the adhesive interaction has been conserved through evolution.

Animals↗
PubMed1985

Involvement of sialic acid on endothelial cells in organ-specific lymphocyte recirculation.

Mouse lymphocytes incubated on cryostat-cut sections of lymphoid organs (lymph nodes and Peyer's patches) specifically adhere to the endothelium of high endothelial venules (HEV), the specialized blood vessels to which recirculating lymphocytes attach as they migrate from the blood into the parenchyma of the lymphoid organs. Treatment of sections with sialidase eliminated the binding of lymphocytes to peripheral lymph node HEV, had no effect on binding to Peyer's patch HEV, and had an intermediate effect on mesenteric lymph node HEV. These results suggest that sialic acid on endothelial cells may be an organ-specific recognition determinant for lymphocyte attachment.

Animals↗