Search results for " Immune system"
showing 10 items of 893 documents
Type II diabetics with macrovascular complications: polymorphonuclear leukocyte (PMN) filtration, PMN membrane fluidity and cytosolic Ca2+ content af…
1998
We evaluated polymorphonuclear (PMN) filtration parameters, membrane fluidity and cytosolic Ca2+ content in 21 normal subjects and in 18 type II diabetics with macrovascular complications (MVC). Evaluations were carried out at baseline and after in vitro activation prolonged for 5 and 15 min. PMA (4-phorbol 12-myristate 13-acetate) and fMLP (N-formyl-methionyl-leucyl-phenylalanine) were used as stimulating agents. TMA-DPH (1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene) was used as fluorescent probe for the membrane fluidity tests and Fura 2-AM for the cytosolic Ca2+ content. A significant variation was evident in PMN filtration parameters at 5 and 15 min. No variation was present i…
Rheological and metabolic leucocyte determinants in diabetes mellitus
1995
In diabetics of type I and 2 we examined, in resting white blood cells (WBC), the filtration parameters (Initial Relative Flow Rate - lRFR, Clogging Rate - CR) employing the St. George Filtrometer, the polymorphonuclear cells (PMN) membrane fluidity, the PMN cytosolic Ca2+ content and the PMN membrane cholesterol/phospholipid ratio (C/PL). From the obtained data, it is evident that, while the lRFR of unfractionated WBC distinguishes normals from diabetics of type 1 and 2, the fIltration parameters of the PMN and mononuclear cells (MN) do not show any significant difference. PMN membrane fluidity, PMN cytosolic Ca2+ content and PMN C/PL do not discriminate normals from diabetics of type 1 an…
Damage-associated molecular pattern activated Toll-like receptor 4 signalling modulates blood pressure in L-NAME-induced hypertension
2013
Aims Recent publications have shed new light on the role of the adaptive and innate immune system in the pathogenesis of hypertension. However, there are limited data whether receptors of the innate immune system may influence blood pressure. Toll-like receptor 4 (TLR4), a pattern recognition receptor, is a key component of the innate immune system, which is activated by exogenous and endogenous ligands. Hypertension is associated with end-organ damage and thus might lead to the release of damage-associated molecular patterns (DAMPs), which are endogenous activators of TLR4 receptors. The present study aimed to elucidate whether TLR4 signalling is able to modulate vascular contractility in …
Apoptotic role of Fas/Fas ligand system in the regulation of erythropoiesis
1999
Abstract The possible involvement of Fas and Fas ligand (FasL) in the regulation of erythropoiesis was evaluated. Immunohistochemistry of normal bone marrow specimens revealed that several immature erythroblasts undergo apoptosis in vivo. Analysis of bone marrow erythroblasts and purified progenitors undergoing unilineage erythroid differentiation showed that Fas is rapidly upregulated in early erythroblasts and expressed at high levels through terminal maturation. However, Fas crosslinking was effective only in less mature erythroblasts, particularly at basophilic level, where it induced apoptosis antagonized by high levels of erythropoietin (Epo). In contrast, FasL was selectively induced…
Repression of Cyclic Adenosine Monophosphate Upregulation Disarms and Expands Human Regulatory T Cells
2011
Abstract The main molecular mechanism of human regulatory T cell (Treg)-mediated suppression has not been elucidated. We show in this study that cAMP represents a key regulator of human Treg function. Repression of cAMP production by inhibition of adenylate cyclase activity or augmentation of cAMP degradation through ectopic expression of a cAMP-degrading phosphodiesterase greatly reduces the suppressive activity of human Treg in vitro and in a humanized mouse model in vivo. Notably, cAMP repression additionally abrogates the anergic state of human Treg, accompanied by nuclear translocation of NFATc1 and induction of its short isoform NFATc1/αA. Treg expanded under cAMP repression, however,…
Adipose tissue lymphocytes: types and roles
2009
Besides adipocytes, specialized in lipid handling and involved in energy balance regulation, white adipose tissue (WAT) is mainly composed of other cell types among which lymphocytes represent a non-negligible proportion. Different types of lymphocytes (B, alphabetaT, gammadeltaT, NK and NKT) have been detected in WAT of rodents or humans, and vary in their relative proportion according to the fat pad anatomical location. The lymphocytes found in intra-abdominal, visceral fat pads seem representative of innate immunity, while those present in subcutaneous fat depots are part of adaptive immunity, at least in mice. Both the number and the activity of the different lymphocyte classes, except …
Regulation of Apoptosis in Endocrine Autoimmunity
2002
Dysregulation of apoptosis is associated with the pathogenesis of organ-specific autoimmune diseases, through altered target organ susceptibility. Apoptosis signaling pathways can be initiated through activation of death receptors such as Fas. A comparative analysis of the expression of Fas and FasL, the antiapoptotic molecule Bcl-2, and apoptosis in both thyrocytes and thyroid-infiltrating lymphocytes (TILs) from patients with either Graves' disease (GD) or Hashimoto's thyroiditis (HT) was performed. GD thyrocytes expressed less Fas than HT thyrocytes, whereas GD TILs had higher levels of Fas and FasL than HT TILs. GD thyrocytes expressed higher levels of Bcl-2 compared with HT thyrocytes.…
Polymorphonuclear leucocyte rheology and cytosolic Ca2+ content after activation in chronic renal failure
2001
SUMMARY: We evaluated polymorphonuclear leucocyte (PMN) flow properties in patients with clinically stable chronic renal failure (CRF) and in control subjects at baseline and after activation with 4-phorbol 12-myristate 13-acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (fMLP). Initial relative flow rate (IRFR) and clogging particles (CPs) were obtained using the St. George's Filtrometer, and PMN membrane fluidity was assessed by marking PMNs with 1-(4-(trimethylamino)phenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH). PMN cytosolic Ca2+ concentration was determined by marking PMNs with Fura 2-AM. At baseline, CRF patients showed a significant increase only in PMN cytosolic Ca2+ content.…
FLT3 as a therapeutic target in AML: still challenging after all these years
2010
Abstract Mutations within the FMS-like tyrosine kinase 3 (FLT3) gene on chromosome 13q12 have been detected in up to 35% of acute myeloid leukemia (AML) patients and represent one of the most frequently identified genetic alterations in AML. Over the last years, FLT3 has emerged as a promising molecular target in therapy of AML. Here, we review results of clinical trials and of correlative laboratory studies using small molecule FLT3 tyrosine kinase inhibitors (TKIs) in AML patients. We also review mechanisms of primary and secondary drug resistance to FLT3-TKI, and from the data currently available we summarize lessons learned from FLT3-TKI monotherapy. Finally, for using FLT3 as a molecul…
Immunoglobulin E (IgE) and ischemic heart disease. Which came first, the chicken or the egg?
2014
Several lines of evidence demonstrate that the immune system plays a pivotal role in development and progression of ischemic heart disease (IHD). More recently, a series of biological and clinical investigations has generated new interest about the existence of a relationship between a specific class of immunoglobulin, that is immunoglobulin E (IgE), and IHD. Data obtained in several epidemiological studies have convincingly demonstrated that the concentration of total serum IgEs is significantly increased in patients with IHD and often correlates with the prognosis. The putative mechanisms are essentially mediated by a physiological interaction between IgEs and mast cells, which triggers t…