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S Jalkanen

Publications and source records attributed to S Jalkanen.

At least 19 recordsLinked to original sources
PubMed1992

Selective endothelial binding of interleukin-2-dependent human T-cell lines derived from different tissues.

The ability of lymphocytes to recognize and bind to high endothelial venules (HEVs) is essential for lymphocyte migration from the blood into lymphoid tissues and into sites of inflammation. Endothelial cell binding capacity also critically determines the clinical usefulness of T-cell lines and clones in immunotherapy. In the present study, interleukin-2-dependent T-cell lines were derived from the blood, lamina propria of the gut, inflamed synovium, synovial fluid, and peripheral lymph nodes. After 3-8 weeks of culture, the expression of homing-associated molecules and binding to mucosal, synovial, and peripheral lymph node HEVs were analyzed. Cell lines derived from the blood and mucosal sites bound significantly better to mucosal and synovial HEVs than to peripheral lymph node HEVs. Three out of seven synovial T-cell lines showed preferential binding to synovial HEVs, whereas the rest bound almost equally well to synovial and mucosal HEVs. T-cell lines from peripheral lymph nodes bound preferentially to lymph node HEVs despite the lack of L-selectin (the peripheral lymph node homing receptor). Expression of the known homing-associated molecules did not predict the HEV-binding specificity of these lines. Importantly, two cell lines bound well to synovial venules, but poorly, if at all, to mucosal or peripheral lymph node HEVs, supporting the concept that synovial-specific HEV recognition mechanisms exist. In conclusion, the tissue origin of T-cell lines critically determines their selectivity for endothelial cell recognition, and besides the known "homing receptors," other molecules may also mediate tissue-specific HEV-binding of interleukin-2-activated T cells.

Antigens, CD↗
PubMed1992

A 90-kilodalton endothelial cell molecule mediating lymphocyte binding in humans.

Interactions between leukocyte surface receptors and their ligands on vascular endothelial cells control lymphocyte traffic between the blood and various lymphoid organs, as well as extravasation of leukocytes into sites of inflammation. A heretofore undescribed 90-kilodalton human endothelial cell adhesion molecule (VAP-1) defined by a monoclonal antibody 1B2 is described. The expression pattern, molecular mass, functional properties, and an amino-terminal amino acid sequence define VAP-1 as an endothelial ligand for lymphocytes. VAP-1 helps to elucidate the complex heterotypic cell interactions that direct tissue-selective lymphocyte migration in man.

Amine Oxidase (Copper-Containing)↗
PubMed1992

Regulation of L-selectin expression on cultured bone marrow leukocytes and their precursors.

L-selectin (LECAM-1, LAM-1, MEL-14 antigen, Dreg antigen) is one of the molecules controlling lymphocyte homing from the blood to peripheral lymph nodes and granulocyte adhesion to inflamed endothelium. In this work, regulation of L-selectin expression on mouse bone marrow cells was studied. L-selectin-negative cells were isolated by panning technique, cultured for 1-7 days with cytokines and mitogens, and L-selectin expression was analyzed by immunofluorescence staining. When cultured for 3 days with interleukin (IL) 1, IL 2, IL 5, IL 6, phytohemagglutinin, pokeweed mitogen or in the medium alone, 75%-85% of L-selectin-negative large cells (including granulocytes, macrophages/monocytes, blasts and their precursors) became L-selectin positive. In contrast, IL 3, IL 4, granulocyte-macrophage colony-stimulating factor (GM-CSF) and lipopolysaccharide (LPS) prevented the induction of L-selectin in a time- and dose-dependent manner. GM-CSF was the most potent inhibitor and only 10%-15% of cells became L-selectin positive after 3 days of culture. Furthermore, L-selectin was down-regulated on cultured unselected bone marrow cells by IL 3, IL 4, GM-CSF and LPS stimulation. After culture, the relative molecular mass of L-selectin was 100 kDa, similar to the size of the granulocyte form of this antigen. Cultured cells adhered to high endothelial venules (HEV) only 10%-32% as effectively as freshly isolated bone marrow cells despite high levels of L-selectin expression. The phenotypic analysis and the HEV binding data indicate that after culturing L-selectin was almost exclusively expressed on bone marrow leukocytes of myeloid series, and on these cells it was not functional in mediating peripheral lymph node HEV binding. Overall, these results show that the expression of L-selectin can be modulated by regulating the maturation and differentiation of the cells in vitro. This supports the idea that different cytokines and mitogens may also be important in controlling migrational status of leukocytes in vivo.

Animals↗
PubMed1992

Proliferating cell nuclear antigen (PCNA) as a prognostic factor in non-Hodgkin's lymphoma.

The prognostic value of immunoperoxidase staining for proliferating cell nuclear antigen (PCNA) was studied in a series of 140 non-Hodgkin's lymphomas with median follow-up of 9 years. Lymphomas where > 50% of cells showed positive staining for PCNA had inferior 5-year survival as compared with those with less than 50% of positive cells (57% vs 41%, P = 0.008). The presence of > 50% of positively staining cells for PCNA was strongly associated with a larger than the median size of the SPF (median, 8.3%), and high histological grade of malignancy (P < 0.0001 for both). Lymphomas with both a large percentage (> 50%) of PCNA positive cells and a larger than the median SPF had inferior outcome as compared with lymphomas where either one or both of these factors were small. Although PCNA staining was not an independent prognostic factor in a multivariate analysis, it appears to be supplementary to the SPF even if determined from old paraffin-embedded tissue material.

Adolescent↗
PubMed1992

Lymphocyte CD44 binds the COOH-terminal heparin-binding domain of fibronectin.

The lymphocyte-high endothelial venule (HEV) cell interaction is an essential element of the immune system, as it controls lymphocyte recirculation between blood and lymphoid organs in the body. This interaction involves an 85-95-kD class of lymphocyte surface glycoprotein(s), CD44. A subset of lymphocyte CD44 molecules is modified by covalent linkage to chondroitin sulfate (Jalkanen, S., M. Jalkanen, R. Bargatze, M. Tammi, and E. C. Butcher. 1988. J. Immunol. 141:1615-1623). In this work, we show that removal of chondroitin sulfate by chondroitinase treatment of lymphocytes or incubation of HEV with chondroitin sulfate does not significantly inhibit lymphocyte binding to HEV, suggesting that chondroitin sulfate is not involved in endothelial cell recognition of lymphocytes. Affinity-purified CD44 antigen was, on the other hand, observed to bind native Type I collagen fibrils, laminin, and fibronectin, but not gelatin. Binding to fibronectin was studied more closely, and it was found to be mediated through the chondroitin sulfate-containing form of the molecule. The binding site on fibronectin was the COOH-terminal heparin binding domain, because (a) the COOH-terminal heparin-binding fragment of fibronectin-bound isolated CD44 antigen; (b) chondroitin sulfate inhibited this binding; and (c) finally, the ectodomain of another cell surface proteoglycan, syndecan, which is known to bind the COOH-terminal heparin binding domain of fibronectin (Saunders, S., and M. Bernfield. 1988. J. Cell Biol. 106: 423-430), inhibited binding of CD44 both to intact fibronectin and to its heparin binding domain. Moreover, inhibition studies showed that binding of a lymphoblastoid cell line, KCA, to heparin binding peptides from COOH-terminal heparin binding fragment of fibronectin was mediated via CD44. These findings suggest that recirculating lymphocytes use the CD44 class of molecules not only for binding to HEV at the site of lymphocyte entry to lymphoid organs as reported earlier but also within the lymphatic tissue where CD44, especially the subset modified by chondroitin sulfate, is used for interaction with extracellular matrix molecules such as fibronectin.

Amino Acid Sequence↗
PubMed1992

Involvement of the avian mu heavy chain in recolonization of the bursa of Fabricius.

In the chicken, the B cells develop in a specialized organ, the bursa of Fabricius. Earlier it was shown that neonatal bursal cells treated with polyclonal anti-chicken immunoglobulin antibodies are not able to recolonize the bursa when transferred into cyclophosphamide-treated chicks. In this study, 4-day-old bursal cells were treated with different polyclonal and monoclonal anti-immunoglobulin antibodies and transferred into 4-day-old cyclophosphamide-treated chickens. Two monoclonal anti-chicken IgM antibodies, CVI-59.7 and 21-2B2, recognizing distinct epitopes of the mu heavy chain, were inhibitory. Incubation of cells with 21-2B2 antibody caused about 90% inhibition of bursal recolonization. After incubation with CVI-59.7 antibody the inhibition was 50%. The high inhibition by 21-2B2 antibody was also seen when F(ab')2 fragments of the antibody were used. These results suggest that the entry of the cells needed for bursal recolonization is inhibited almost totally by 21-2B2 antibody, or that this antibody blocks further proliferation of the cells in bursal follicles. In conclusion, we have shown that a mu heavy chain epitope is intimately involved in the recolonization of bursal follicles, and distinct epitopes of the mu heavy chain are not equally important in this process.

Animals↗
PubMed1992

Macrophages, T cell receptor usage, and endothelial cell activation in the pancreas at the onset of insulin-dependent diabetes mellitus.

Current knowledge of the phenotype of mononuclear cells accumulating in pancreatic islets in insulin-dependent diabetes (IDDM) and factors determining their homing into the pancreas is limited. Therefore, a pancreas obtained at the onset of IDDM was studied in detail. Cryostat sections were stained for mononuclear cell types, T cell receptor subtypes, and adhesion molecules of vascular endothelium and studied by immunofluorescence microscopy, and peripheral blood mononuclear cells were phenotyped using flow cytometry. Monocytes/macrophages (lysozyme- or CD 14-reactive cells) were identified among other mononuclear cell types in islet infiltrates. V beta 8-positive T cells were overrepresented, but T cells with other V beta s studied (V beta 5, V beta 5.1, V beta 6, V beta 12) were also found. The vascular endothelium of the islets and many small vessels nearby islets strongly expressed intercellular adhesion molecule-1, whereas vascular cell adhesion molecule-1 and E-selectin were totally absent. We conclude: (a) that increased expression of intercellular adhesion molecule-1 on vascular endothelium may increase endothelial adhesion of mononuclear cells and enhance their accumulation in the pancreas during diabetic insulitis; (b) that T cells with certain T cell receptors can be enriched in infiltrated pancreatic islets; and (c) that macrophages and antigen-specific CD 8-positive T cells are involved in pancreatic beta cell destruction at the onset of IDDM.

Antigens, CD↗
PubMed1991

Comparison of S-phase fraction, working formulation, and Kiel classification in non-Hodgkin's lymphoma.

The prognostic value of S-phase fraction (SPF), determined by flow cytometric study from paraffin-embedded tissue, and grading by Working Formulation (WF) and Kiel classification were compared among 245 patients with non-Hodgkin's lymphoma followed for the median of 89 months or until death. Histologic reclassification and SPF determinations were done without knowledge on clinical data. SPF (P equals 0.0001), WF (P equals 0.0003), and Kiel classification (P equals 0.0008) were associated with mortality in lymphoma in a univariate analysis, and WF and SPF were independent prognostic factors in Cox's multivariate analysis. Although SPF correlated strongly both with WF and Kiel grades (P less than 0.0001), low-grade and high-grade malignant lymphomas according to Kiel classification, and high-grade lymphomas according to WF could be divided into groups with significantly different outcome by SPF. The results suggests a role for SPF in therapeutic decision-making.

Adolescent↗
PubMed1991

Intracellular pathogens and professional phagocytes in reactive arthritis.

Reactive arthritis is a postinfectious complication which develops after certain infections, mostly gastrointestinal or urogenital. Antigenic structures of the causative microbes, but no live organisms, have been demonstrated in inflamed joints. The host factors as well as the microbial antigens responsible for the initiation of the arthritic process are unknown. The pathogenesis of reactive arthritis is discussed here with special reference to the intracellular life of the causative microbes and to monocytes/macrophages, which may be involved in early events of the arthritic process as well as in maintenance of the autoimmune type of responses.

Antigens, Bacterial↗
PubMed1991

Lymphocyte homing and clinical behavior of non-Hodgkin's lymphoma.

Lymphocyte homing receptors (HRs) defined by Hermes antibodies (anti-CD44) and lymphocyte function associated antigen-1 (LFA-1, CD11a/CD18) are involved in lymphocyte binding to endothelial cells of high endothelial venules (HEVs) at sites where lymphocytes exit the blood. Their expression was correlated to the clinical behavior of 245 non-Hodgkin's lymphomas followed up for the median of 87 mo after the diagnosis. Lymphomas that showed no or weak staining intensity for HRs were more often of stage I (P = 0.005), disseminated less frequently hematogenously (P = 0.003), and had more favorable prognosis than lymphomas with intensive staining for HRs (P less than 0.0001) despite that they were more often histologically of high grade malignancy (P = 0.002). Expression of LFA-1 beta chain (CD18) did not correlate significantly with stage or survival, but had prognostic value in a subgroup of HR expression negative lymphomas (P = 0.03). HR staining intensity was an independent prognostic factor in a multivariate analysis. These findings indicate that Hermes/CD44 molecule is associated to the determination of the metastatic potential and prognosis of non-Hodgkin's lymphomas. They also reveal a new entity among non-Hodgkin's lymphomas, because lymphomas that express low levels of HR have favorable prognosis despite their often highly malignant histological appearance.

Adolescent↗
PubMed1991

Regulation of lymphocyte traffic to mucosa-associated lymphatic tissues.

Lymphocyte recognition and binding to endothelial cells at sites where lymphocytes exit the blood is controlled by several molecules. At mucosal sites, the lymphocytes use at least VLA-4, CD44, and LFA-1 (CD18/CD11a) to bind the endothelial cell ligand molecules. The endothelial cell surface ligand for CD44 is probably a human equivalent of MECA-367 and hyaluronate. LFA-1 can bind to ICAM-1/ICAM-2; and VLA-4, to VCAM-1 on endothelium. However, for physiologic lymphocyte migration, these molecules may still need additional ligands that are currently uncharacterized. At sites of inflammation, cytokines increase the expression of ICAM-1, VCAM-1, and a third endothelial cell antigen, ELAM-1, whose counter-receptor on leukocyte surface is presently unknown. Upregulation of these molecules apparently facilitates the traffic of lymphocytes and other leukocytes to sites of inflammation, thus partially determining the nature and extent of inflammation. These same molecules may be equally responsible for the pathologic characteristics of the immune response seen, for example, in inflammatory bowel diseases.

Animals↗
PubMed1990

Bursectomy of chicken embryos at 60 hours of incubation leads to an oligoclonal B cell compartment and restricted Ig diversity.

Chickens that have been surgically bursectomized at 60 h of embryonic development usually generate Ig producing B cells; however, the bursectomized chickens are incapable of specific antibody responses, even after repeated immunization. In the present work, we analyzed the molecular basis of this immunodeficiency. In the bursectomized chickens, DNA sequencing revealed a repertoire of Ig L and H chains with a low number of different V-J and V-D-J joints, indicating an oligoclonal B cell compartment. In addition, the L and H chains belonging to each B cell clone had similar gene conversion events in the V region. In situ hybridization to Harderian gland tissue sections showed, that B cells of the bursectomized chickens were, however, capable of terminal plasma cell maturation. Thus, in chickens that were lacking the bursal microenvironment, 1) only a few B cell precursors differentiated into mature Ig-producing B cells, 2) low rate of gene conversion resulted in restricted Ig diversity. Regarding the chicken B cell differentiation, the present data support a model that the induction of B cell differentiation is a bursa-independent event, whereas the bursa of Fabricius has a crucial role in the amplification and diversification of the embryonic B cell repertoire.

Amino Acid Sequence↗
PubMed1990

Biologic progression in non-Hodgkin's lymphoma. A flow cytometric study.

The nuclear DNA content of 37 primary non-Hodgkin's lymphomas both at presentation and at relapse was determined by flow cytometric analysis from paraffin-embedded tissue to investigate changes in DNA ploidy and S-phase fraction (SPF) during the course of the disease, and their association with survival. The repeat biopsies were done from 5 months to 15 years after the diagnosis. Four low-grade lymphomas according to the Working Formulation transformed into intermediate-grade lymphomas (four of 11, 36%), and four intermediate-grade lymphomas into high-grade lymphomas during the follow-up (four of 16, 25%), and five of these eight transformed lymphomas were fatal within 18 months after relapse. The SPF correlated strongly with poor prognosis if measured either from the primary biopsy (P = 0.008), the first (P = 0.009), or the latest repeat biopsy (P = 0.006). If SPF was greater than or equal to 6% larger in a repeat biopsy than at presentation prognosis was poor; six of nine such patients died from lymphoma within 11 months from recurrence. An increase of greater than or equal to 6% in the SPF was more common in high-grade (four of nine, 44%) and intermediate-grade (four of 16, 25%) lymphomas than in low-grade lymphomas (one of 11, 9%), and it was occasionally (three of nine) associated with a morphologic change. In a few cases a repeat biopsy was diploid despite DNA aneuploidy at presentation. In conclusion, the study provides evidence that not only may low-grade lymphomas transform into higher grade lymphomas, but high-grade lymphomas may also frequently transform into more malignant forms during the course of the disease. The SPF is useful in monitoring the biological behavior of non-Hodgkin's lymphoma, and it appears to give information not obtained by histologic study alone.

Adult↗
PubMed1990

Prognostic value of lymphocyte homing receptor and S phase fraction in non-Hodgkin's lymphoma.

Lymphocyte homing receptors (HRs) mediate lymphocyte binding to high endothelial venules, and control their circulation between the blood and the lymphoid organs. The role of HRs and nuclear DNA content in the spread and prognosis of non-Hodgkin's lymphoma was studied from paraffin-embedded tumor sections of 104 patients followed-up for the minimum of 5 years after the diagnosis. HR expression was analyzed by staining with a monoclonal antibody, Hermes-3, and DNA content by flow cytometry. Ten (10%) lymphomas were HR negative (HR-), 14 (13%) weakly (HR+/-), and 80 (77%) strongly positive (HR+). HR- lymphomas disseminated less often than HR+/- or HR+ lymphomas (P = .03), and their prognosis was more favorable (P = .03), although they often had a large S phase fraction (SPF), indicating a rapid proliferation rate. A large SPF (greater than 12%) was strongly associated with an unfavorable histologic type in Working Formulation (P = .0001) and poor survival (P = .006), whereas DNA aneuploidy was not. The 5-year survival rate corrected for intercurrent deaths was 61% in lymphomas with SPF less than 12% or with HR-, but only 15% if SPF was greater than 12% and HR+ (P less than .0001). In multivariate analysis stage (P less than .001), SPF (P = .002) and HR (P = .003) were the only independent prognostic factors.

Adult↗
PubMed1990

Salmonella lipopolysaccharide in synovial cells from patients with reactive arthritis.

Synovial cells from nine patients with reactive arthritis following Salmonella enteritidis or Salmonella typhimurium infection were examined for salmonella antigens. Extensive bacterial cultures of the synovial fluid were negative. Eight synovial-fluid cell samples stained positively on immunofluorescence with rabbit antisera against heat-killed S enteritidis or S typhimurium or with monoclonal antibodies specific for the causative salmonella lipopolysaccharide (LPS). Synovial tissue from the ninth patient stained positively in the avidin-biotin-peroxidase complex method with the monoclonal antibody. Control samples (synovial-fluid cells from thirteen patients with other rheumatic diseases and synovial tissue from two) were negative. Synovial cells from eight patients and five controls were studied by western blotting with the same monoclonal antibodies. Four of the eight patients but no controls had blots indicating salmonella LPS in the synovial cells. The presence of bacterial LPS in the joint is a common and pathogenetically important feature of reactive arthritis.

Acute Disease↗