Search PubMed⌕ Search

Biomedical subjects

H Helin

Publications and source records attributed to H Helin.

At least 91 records · Page 5Linked to original sources
PubMed1986

Monocyte procoagulant inducing factor: a lymphokine involved in the T cell-instructed monocyte procoagulant response to antigen.

A T cell-derived lymphokine couples the recognition of alloantigens by human T inducer cells to monocyte effector procoagulant activity (PCA). This collaborative cellular response results in expression of the functional tissue factor gene product and initiation of the extrinsic coagulation protease cascade as an inflammatory sequelae to the immune response. We now provide initial characterization of this lymphokine, provide evidence that it is a unique lymphokine, and designate it as monocyte procoagulant inducing factor (MPIF). MPIF was produced by alloantigen-stimulated, nylon wool-purified T cells and was not diminished by irradiation. MPIF active supernatants induced PCA in isolated monocytes, and the effect was not modified by the presence of T cells with the responding monocytes, consistent with a direct effect on the monocyte effector cells rather than an indirect effect via an intermediate accessory T cell. Full expression of PCA by monocytes was complete within 4 to 6 hours. MPIF activity in mixed lymphocyte culture (MLC) supernatants (MLC-SN) was stable at pH 2.0 for 24 hr, but was diminished after exposure to pH 10.5 for 30 min. MPIF activity was stable at 56 degrees C but was labile at 63 degrees C or higher. When characterized by chromatography on Sephadex G-100 superfine at either pH 7.2 or 3.6, the activity was recovered in a major discrete peak of about 55,000 daltons, and minor peaks of activity at about 14,000 and greater than 150,000 daltons. There was no correlation between the presence or concentration of INF-gamma, INF-alpha, IL 1, IL 2, GM-CSF, CSF-1, TNF-alpha, TNF-beta (lymphotoxin), or migration inhibitory factor (MIF) with MPIF activity. Each of the previously defined cytokines was analyzed directly for MPIF activity. INF-gamma, INF-alpha, GM-CSF, TNF-alpha, and CSF-1 did not possess MPIF activity over a wide range of concentrations. IL 1 and IL 2 lacked activity at concentrations present in MLC medium positive for MPIF; however, at higher concentrations each demonstrated slight activity. There was a poor correlation between MPIF and MIF activities in MLC-SN, and the content of MIF was insufficient to account for the expressed level of MPIF activity. The lack of identity of these cytokines with MPIF was supported by selected MLC medium that lacked IL 1, IL 2, and MIF and yet contained high MPIF activity. MPIF was additionally distinguished from IL 1, IL 2, and MIF on the basis of separation in Sephadex G-100 superfine.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Coagulation Factors↗
PubMed1986

Activation of complement by intermediate filaments of glomerular epithelial cells.

Glomerular visceral epithelial cells, podocytes, have been shown by immunofluorescence and immunoperoxidase staining methods to bind serum complement (C) components in vitro. Binding of Clq, C4, and C3 was demonstrated and the C4 and C3 binding could be inhibited by EDTA. Thus complement binding had the capacity to cause antibody-independent activation of the "classical" C pathway. The C-binding structures had the same distribution as intermediate filaments (IMFs) of vimentin but not desmin or keratin types. By ultrastructural immunohistochemical staining C3 was observed in association with cytoskeletal IMFs.

Complement Activation↗
PubMed1986

Rheumatoid factor in rheumatoid arthritis associated renal disease and in lupus nephritis.

To test the hypothesis that rheumatoid factor (RF) protects against (immune complex mediated) renal disease, patients with rheumatoid arthritis (RA; 48 with nephropathy of various types, 35 without renal disease) and systemic lupus erythematosus (SLE; 35 with and 17 without nephritis) were evaluated for the presence and titre of RF. There was no correlation between RF and nephropathy in RA, whereas in SLE RFs were almost exclusively seen in patients without nephropathy. This result supports the above hypothesis for lupus nephropathy but not for RA associated renal disease, and it may be explained by a more pronounced role for immune complexes in SLE and interference of RFs with the complexes.

Arthritis, Rheumatoid↗
PubMed1986

Mild mesangial glomerulopathy--a frequent finding in rheumatoid arthritis patients with hematuria or proteinuria.

Renal biopsy specimens from 39 patients with rheumatoid arthritis and clinical signs of renal disease disclosed a mild mesangial glomerulopathy in more than 1 in 4 cases. Almost all patients had deposits of immunoglobulin and complement in the mesangial lesions. This type of glomerulopathy was the most common cause of hematuria and was also frequently encountered in proteinuric patients. Clinically it was not possible to distinguish between mesangial and membranous nephropathy.

Adult↗
PubMed1986

Macrophage procoagulant factors--mediators of inflammatory and neoplastic tissue lesions.

Mononuclear phagocytes, a specialized cell lineage comprising bone-marrow precursors, blood monocytes and tissue macrophages, can interact with blood coagulation mechanisms with resulting thrombus formation or extravascular fibrin accumulation. Such procoagulant activity is usually activation dependent and requires interaction of the cells with immune or nonimmune stimuli. In the former case (e.g., alloantigens, soluble protein antigens) collaboration of mononuclear phagocytes with T lymphocytes is necessary and is mediated by cell-to-cell contact or lymphokines. Prototype of a direct acting stimulus is bacterial lipopolysaccharide. Mononuclear phagocyte procoagulant activity is expressed in the form of cell membrane-bound or released factors which display molecular heterogeneity. They include the initiator of the extrinsic clotting pathway, tissue factor, known clotting proteases such as factors V and VII, and novel proteolytic enzymes including prothrombinase and a factor X activator. Mononuclear phagocyte procoagulants are pathogenetically involved in generalized disorders with intravascular coagulation and thromboembolic phenomena. These disorders, exemplified by the Shwartzman reaction and possibly by paraneoplastic thromboembolism, are initiated by blood monocytes. Extravascular fibrin deposition can be initiated by tissue-infiltrating monocytes and macrophages in disease states such as acute renal allograft failure and solid tumours.

Animals↗
PubMed1985

Clinicopathologic correlations in a series of 143 patients with IgA glomerulonephritis.

In an unselected series of patients with IgA glomerulonephritis, old age, high blood pressure, and high urinary protein excretion at the time of renal biopsy were found to correlate with impaired renal function, whereas sex, estimated duration of the disease, or high serum IgA levels did not. The following clinical features were favorable prognostic signs: asymptomatic proteinuria, macroscopic hematuria, and isolated microscopic hematuria. The degree of diffuse mesangial alteration and the presence of segmental glomerular lesions correlated clearly with the subsequent clinical outcome. Vascular lesions, i.e. arteriosclerosis and renal vascular deposition of C3, were most often present in patients with severe glomerulopathy. The presence of electron-dense deposits in glomerular capillary walls was also an unfavorable prognostic finding. Renal biopsy findings of interstitial infiltrates of inflammatory cells and IgA distributed along glomerular capillary walls were usually associated with extrarenal manifestations of the disease.

Adolescent↗
PubMed1985

Immunohistochemical localization of human liver specific protein using rabbit antisera and the avidin-biotin complex technique.

A sensitive enzymatic avidin-biotin complex technique was utilized to locate the antigenic sites in human liver which react with rabbit antibodies to human liver specific protein (LSP). Depending on the rabbit antiserum used, anti-LSP reactive material was seen in different locations. (1) diffusely distributed in liver parenchymal cells, (2) in both hepatocyte cytoplasm and plasma membrane and (3) in hepatocyte plasma membrane only. The cytoplasmic staining was partially or totally abolished by preabsorption with human kidney homogenate whilst the plasma membrane staining remained uninfluenced. The latter was apparently confined to bile canalicular walls and may be liver specific in contrast to the cytoplasmic reaction which seems to be due to antigen determinants cross-reacting with tissue components in kidney.

Animals↗
PubMed1984

Renal biopsy in acute renal failure.

Renal biopsies were performed on 91 out of 99 patients with acute intrinsic renal failure. In all these 91 cases a clinical diagnosis was suggested by an experienced nephrologist unaware of the renal biopsy findings. Most diagnoses agreed with the histopathological findings, but there were important exceptions. On clinical grounds, acute tubulointerstitial renal disease was diagnosed correctly in 77% and acute glomerulonephritis in 56%. In 15% of the patients the clinical data did not permit any certain diagnostic suggestion. In about 20% the biopsy finding definitely influenced the choice of medical treatment. In those 15 patients who needed dialysis treatment, the biopsy findings helped in determining whether this need was temporary or permanent. Our results show that renal biopsy is valuable in settling the diagnosis, in determining the prognosis, and in planning the treatment of acute intrinsic renal failure.

Acute Kidney Injury↗
PubMed1984

A distinct "slow" cellular pathway involving soluble mediators for the T cell-instructed induction of monocyte tissue factor activity in an allogeneic immune response.

Allogeneic stimulation of human lymphoid cells initiates a collaborative cellular pathway that relatively rapidly induces in monocytes the synthesis and cell surface expression of tissue factor, the initiating cofactor of the extrinsic coagulation pathway. T cells are required for the monocyte procoagulant generation, because the addition of autologous or allogeneic T cells fully reconstitutes the activity in otherwise nonresponding highly purified monocytes. Despite a strict T cell requirement, only low T cell to monocyte ratios are necessary for maximal PCA response. Our results further demonstrate that the collaborative signal from allogeneically stimulated T cells to effector monocytes is transferred by a soluble mediator rather than direct cell to cell contact. Other aspects of the present study include the observation that among normal peripheral blood lymphoid cells, monocytes elicit the strongest allogeneic PCA response. This response is clearly exceeded by that induced upon stimulation with Daudi lymphoblastoid B cells. Our data demonstrate the existence of a second distinct cellular pathway that mediates the lymphoid procoagulant response. This pathway differs from the previously characterized response to bacterial LPS in respect to: a) kinetics of T cell triggering; b) mediation by a soluble product; c) lack of genetic restriction of T cell; monocyte collaboration; and d) deficient capacity for direct T cell induction of the monocyte PCA response.

B-Lymphocytes↗
PubMed1983

Allogeneic induction of the human T cell-instructed monocyte procoagulant response is rapid and is elicited by HLA-DR.

The recognition of alloantigens by human lymphoid cells initiates a collaborative cellular pathway that rather rapidly induces in adherent cells (monocytes) the synthesis and expression of cell surface tissue factor, the initiating cofactor of the extrinsic coagulation pathway. This response was vigorous, generating tissue factor to a level nearly comparable to the response to endotoxin. However, it was temporally discordant with characterized lymphoid procoagulant responses to endotoxin, virus, and immune complexes in that it reached a maxima at 48 h, well after these other responses but clearly much faster than the well recognized proliferative responses to allogeneic stimulation. Using the Daudi lymphoblastoid B cell line, the allogeneic response could be fully elicited in a dose-dependent fashion within 18 h. The induction of monocyte tissue factor required collaboration with T lymphocytes, in accord with previously described T cell-instructed monocyte responses. HLA-DR was implicated as the allogeneic signal by the ability of two monoclonal antibodies to completely block, in a dose-dependent fashion, the induction of this pathway. Notably, the allogeneic procoagulant response was quantitatively discordant with respect to the allogeneic proliferative response, suggesting differences in specificity. This relatively rapid response may be applicable to typing of determinants in the major histocompatibility complex that are not equivalently identified by alternative analyses, and may be significant in tissue transplantation. The cellular pathway, linking allogeneic recognition with induction of a monocyte response that initiates the coagulation pathway, represents a further example of the linkage between these biologic systems, and is consistent with a pathogenetic role in allograft rejection by the promotion of vascular thrombosis and interstitial fibrin accumulation.

Antibodies, Monoclonal↗
PubMed1983

Renal involvement and circulating immune complexes in dermatitis herpetiformis.

A fine-needle kidney biopsy was performed on eleven patients with dermatitis herpetiformis (DH) who had no previous signs or symptoms of renal disease. Of the eight patients whose biopsy specimens were representative, electron microscopic examination showed mesangial deposits in five. A subsequent conventional renal biopsy was obtained from one of these five, and immunofluorescence microscopy revealed IgA and complement deposits in the glomeruli. Renal involvement was not related either to the degree of jejunal villous atrophy or to the deposition of IgA and complement in the skin. Glomerular deposits, however, were associated with a high frequency of circulating IgA and IgG class immune complexes and IgA class antigliadin and antireticulin antibodies. These results suggest that, in DH, immune complexes or antibodies derived from the gut can be deposited in the kidney.

Adult↗
PubMed1983

Complement-mediated binding of monocytes to intermediate filaments in vitro.

An in vitro model for complement (C)-mediated monocyte binding to injured cells is described. This model is based on the property of cytoskeletal intermediate filaments (IMF) to directly and independently activate serum C via the classic pathway. Fixed monolayers of cultured fibroblasts, endothelial cells, and L 132 epithelial cells were each used as targets. The authors first subjected the target cells to limited detergent extraction in order to make permeable the plasma membrane, and then exposed them to normal human serum. Immunohistologic analysis demonstrated that this process permitted binding of clearly demonstrable amounts of C1q, C4, and C3 to cytoplasmic loci containing IMF. The target cells were then incubated for various lengths of time with peripheral blood mononuclear cells containing about 20% monocytes. Preferential binding of monocytes was demonstrated by histochemical and immunologic staining methods. Only 5% of the attached cells were B lymphocytes. By transmission electron microscopy the attached cells exhibited typical monocyte morphology. Attachment to target cells involved contact with areas rich in IMFs and led to signs of activation; both an increased number of cytoplasmic organelles and phagocytosis of target cell material were observed. Attachment of monocytes was clearly dependent on serum treatment of the targets; the ratio was 10:1 when compared with control experiments using target cells that had not been incubated with serum. It is reasonable to consider that bound monocyte-derived macrophages associate with activated C components, most likely C3b fragments or C1q, for which monocyte surface receptors have been established. This mechanism may be triggered in various inflammatory reactions involving cell and tissue injury and as an event in the final stages of macrophage-mediated removal of injured or nonviable cells.

Animals↗