Receptor Mediated Binding of the Fibrinolytic Components, Plasminogen and Urokinase, to Peripheral Blood Cells

SummaryGlu-plasminogen binds to platelets; the monocytoid line, U937, and the human fetal fibroblast line, GM1380 bind both plasminogen and its activator, urokinase. This study assesses the interaction of these fibrinolytic proteins with circulating human blood cells. Plasminogen bound minimally to red cells but bound saturably and reversibly to monocytes, granulocytes and lymphocytes with apparent Kd values of 0.9-1.4 μM. The interactions were of high capacity with 1.6 to 49 × 105 sites/cell and involved the lysine binding sites of plasminogen. Both T cells and non-rosetting lymphocytes and two B cell lines saturably bound plasminogen. Urokinase bound saturably to gianulocytes, monocytes, non-rosetting lymphocytes and a B cell line, but minimally to T cells, platelets and red cells. Therefore, plasminogen binding sites of high capacity, of similar affinities, and with common recognition specificities are expressed by many peripheral blood cells. Urokinase receptors are also widely distributed, but less so than plasminogen binding sites. The binding ol plasminogen and/ or urokinase to these cells may lead to generation of cell- associated proteolytic activity which contributes to a variety of cellular functions.

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Impact of Short-Term Systemic Hypoxia on Phagocytosis, Cytokine Production, and Transcription Factor Activation in Peripheral Blood Cells

Mediators of Inflammation ◽

10.1155/2011/429501 ◽

2011 ◽

Vol 2011 ◽

pp. 1-9 ◽

Cited By ~ 16

Author(s):

Michael Fritzenwanger ◽

Christian Jung ◽

Bjoern Goebel ◽

Alexander Lauten ◽

Hans R. Figulla

Keyword(s):

Peripheral Blood ◽

Blood Cells ◽

Cytokine Production ◽

Interferon Γ ◽

Peripheral Blood Cells ◽

Immune Functions ◽

Cellular Functions ◽

Short Term ◽

Transcription Factor Activation ◽

Systemic Hypoxia

Hypoxia frequently associated with certain physiologic and pathologic conditions influences numerous cellular functions. Because the effects of short-term hypoxia are incompletely understood, we examined phagocytosis and cytokine production as well as the activation of the transcription factors HIF-1 and NFκB in peripheral blood cells of healthy volunteers exposed to an oxygen concentration equivalent to that found at a height of 5500 m. Furthermore, we analysed plasma HIF-1 and serum concentrations of various HIF-1-dependent genes. Results showed that short-term hypoxia increased phagocytosis in neutrophils without affecting monocyte phagocytosis. Hypoxia decreased basal TNFα concentration in monocytes and basal interferon γ concentration in CD4+T lymphocytes. In contrast, plasma HIF and serum VEGF concentrations were not affected by hypoxia, although serum EPO concentration was raised. In PBMC, hypoxia increased cytosolic HIF-1 concentration without affecting nuclear HIF-1 concentration and led to a rise in the nuclear NFκB in PBMC. Our results show that short-term hypoxia affects immune functions in healthy individuals. Furthermore, we speculate that the effects of hypoxia are not due to HIF-1, but are caused by the activation of NFκB .

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Allogeneic Donor NK Cell Infusion and IL-2 for Patients with Refractory B-Cell Non-Hodgkin Lymphoma.

Blood ◽

10.1182/blood.v114.22.3036.3036 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3036-3036

Author(s):

Veronika Bachanova ◽

Linda J. Burns ◽

David H. McKenna ◽

Julie Curtsinger ◽

Sarah Cooley ◽

...

Keyword(s):

B Cell ◽

Nk Cells ◽

Peripheral Blood ◽

Blood Cells ◽

Cell Expansion ◽

Nk Cell ◽

Peripheral Blood Cells ◽

Non Hodgkin Lymphoma ◽

Pre Treatment

Abstract Abstract 3036 Poster Board II-1012 The potential role of allogeneic natural killer (NK) cells for therapy of refractory lymphoma is supported by the curative potential of allogeneic transplantation for lymphoid malignancies. Haploidentical donor derived NK cells may overcome Class I MHC Ag mediated inhibition and deliver an NK versus lymphoma effect. In a Phase II study we evaluated allogeneic NK cell infusions with Rituximab and IL-2 in a non-transplant setting to determine the expansion of NK cells in vivo and the clinical response in patients with refractory B-cell non-Hodgkin lymphoma (NHL). Six patients with advanced NHL received conditioning with Rituximab 375mg/m2 days -8,-1,+6,+15; Cyclophosphamide 60 mg/kg IV day -5; Fludarabine 25 mg/m2 IV days -6 through -2 as immunosupression to permit homeostatic expansion of allogeneic donor NK cells. Peripheral blood cells were obtained by lymphapheresis from unmobilized, HLA-haploidentical donors and selected for “killer immunoglobulin receptor” (KIR) ligand mismatch when available (3 out of 6 patients). Donor peripheral blood cells were enriched for NK cells with the Miltenyi CliniMACS device by depletion of T (CD3+) cells. The donor NK cells were then activated by overnight incubation with IL-2 (1,000 U/mL) and infused at a median nucleated cell dose of 2.27 ±0.4 × 107/kg. Subcutaneous IL-2 10×106 units (qod x 6 doses) was given to facilitate NK cell survival and expansion. All patients were evaluable for toxicity and efficacy. Patients tolerated the NK infusion well with only transient grade 1-2 toxicity and 5 received all 6 scheduled doses of IL-2. IL-2 activated donor NK cell products showed > 55% cytotoxicity against K562 targets. After IL-2 therapy, we observed a median absolute lymphocyte count of 980 ±440/μL. All cells were of recipient origin with no detectable donor NK cells. Importantly, in all patients the median number of host regulatory T cells (T regs phenotype CD4+Foxp3+CD127−) post treatment was significantly increased compared to pre-treatment (day 14 T regs: 134 ±141 cells/μL versus pre-treatment T regs: 24 ±12 cells/μL; P=0.06). To investigate the possibility of NK trafficking to affected lymph nodes, we performed fine needle aspiration of palpable tumor in 1 patient and demonstrated a low level of donor DNA by RFLP testing (2.5% donor chimerism). Simultaneous absence of NK cells in peripheral blood in the same patient suggested NK cell tissue homing to lymphoma-bearing nodes. Three patients achieved a partial remission (PR), one of whom proceeded to non-myeloablative cord blood allograft 2 month after NK cell infusion; two remain in partial remission after 1 and 4 months of follow-up. The trial failed to achieve prospective statistical parameters established to detect circulating NK cell expansion rate and will be modified. Conclusions This “proof of principle” study demonstrated lack of in vivo expansion of haploidentical NK cells in peripheral blood of patients with lymphoma. However, we identified host factors that interfered with NK cell expansion, including T reg proliferation and possibly inadequate immunosupression, and additionally, the finding of donor DNA in sites of tumor suggested donor NK cell localization to extravascular or tumor sites. Novel approaches to adoptive NK cell therapy trials should incorporate strategies to eliminate or prevent T reg expansion using alternate lymphodepleting regimens. Disclosures No relevant conflicts of interest to declare.

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In vitro synthesis of antibodies to acetylcholine receptor by peripheral blood cells: Role of suppressor T cells in normal subjects

Neurology ◽

10.1212/wnl.34.6.802 ◽

1984 ◽

Vol 34 (6) ◽

pp. 802-802 ◽

Cited By ~ 21

Author(s):

R. P. Lisak ◽

C. Laramore ◽

A. I. Levinson ◽

B. Zweiman ◽

A. R. Moskovitz ◽

...

Keyword(s):

T Cells ◽

Acetylcholine Receptor ◽

Peripheral Blood ◽

Blood Cells ◽

Normal Subjects ◽

Peripheral Blood Cells ◽

Suppressor T Cells ◽

In Vitro Synthesis

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Studies on the supression of normal B-cell maturation by peripheral blood cells from patients with acquired hypogammaglobulinemia and from normal neonates

Clinical Immunology and Immunopathology ◽

10.1016/0090-1229(76)90084-2 ◽

1976 ◽

Vol 6 (3) ◽

pp. 312-317 ◽

Cited By ~ 7

Author(s):

S.B. Witemeyer ◽

A.D. Bankhurst ◽

R.C. Williams

Keyword(s):

B Cell ◽

Peripheral Blood ◽

Blood Cells ◽

Cell Maturation ◽

Peripheral Blood Cells ◽

B Cell Maturation ◽

Normal Neonates

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Anti-tumor cytotoxicity of γδ T cells expanded from peripheral blood cells of patients with myeloma and lymphoma

Medical Oncology ◽

10.1007/s12032-007-9004-4 ◽

2007 ◽

Vol 25 (2) ◽

pp. 137-147 ◽

Cited By ~ 29

Author(s):

Anri Saitoh ◽

Miwako Narita ◽

Norihiro Watanabe ◽

Nozomi Tochiki ◽

Noriyuki Satoh ◽

...

Keyword(s):

T Cells ◽

Peripheral Blood ◽

Blood Cells ◽

Γδ T Cells ◽

Peripheral Blood Cells ◽

Tumor Cytotoxicity

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pattern of cytokine secretion by peripheral blood cells of patients with multiple sclerosis in Brazil

Multiple Sclerosis Journal ◽

10.1177/135245850000600501 ◽

2000 ◽

Vol 6 (5) ◽

pp. 293-299 ◽

Cited By ~ 3

Author(s):

Patrícia Mara da Costa ◽

Clarissa Lin Yasuda ◽

Silvia M Scagliusi ◽

Blanca Maria Diaz-Bardales ◽

Ernane Maciel ◽

...

Keyword(s):

Multiple Sclerosis ◽

T Cells ◽

Inflammatory Cytokines ◽

Peripheral Blood ◽

Blood Cells ◽

Basic Protein ◽

Chronic Phase ◽

Peripheral Blood Cells ◽

Activated T Cells ◽

Organ Specific

Autoimmune T cells play a key role as regulators and effectors of organ-specific autoimmune disease. In multiple sclerosis (MS), activated T cells specific for myelin components produce a plethora of inflammatory cytokines and mediators that contribute to myelin damage. The production of proinflammatory and regulatory cytokines by peripheral blood cells from patients with active and stable MS and healthy controls were examined. The results show that TNFa production was somewhat elevated in active MS with no significant increase in the level IFNg, whereas in the chronic phase the anti-inflammatory cytokines IL-10 and TGFb increased, accompanied by a reduction in IFNg when stimulated by myelin basic protein.

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