scholarly journals Enhanced Adhesive Capacities of the Naturally Occurring Ile249–Met280Variant of the Chemokine Receptor CX3CR1

2004 ◽  
Vol 279 (19) ◽  
pp. 19649-19657 ◽  
Author(s):  
Mehdi Daoudi ◽  
Elise Lavergne ◽  
Alexandre Garin ◽  
Nadine Tarantino ◽  
Patrice Debré ◽  
...  
Keyword(s):  
G Protein ◽  
Calcium Release ◽  
Mononuclear Cells ◽  
Binding Capacity ◽  
Flow Chamber ◽  
Soluble Form ◽  
Peripheral Blood Mononuclear ◽  
Naturally Occurring ◽  
Aspiration Technique ◽  
Membrane Bound

It was recently shown that individuals carrying the naturally occurring mutant CX3CR1-Ile249–Met280(hereafter called CX3CR1-IM) have a lower risk of cardiovascular disease than individuals homozygous for the wild-type CX3CR1-Val249–Thr280(CX3CR1-VT). We report here that peripheral blood mononuclear cells (PBMC) from individuals with the CX3CR1-IM haplotype adhered more potently to membrane-bound CX3CL1 than did PBMC from homozygous CX3CR1-VT donors. Similar excess adhesion was observed with CX3CR1-IM-transfected human embryonic kidney (HEK) cell lines tested with two different methods: the parallel plate laminar flow chamber and the dual pipette aspiration technique. Suppression of the extra adhesion in the presence of pertussis toxin indicates that G-protein mediated the underlying transduction pathway, in contrast to the G-protein-independent adhesion previously described for CX3CR1-VT. Surprisingly, HEK and PBMC that expressed CX3CR1-IM and -VT were indistinguishable when tested with the soluble form of CX3CL1 for chemotaxis, calcium release, and binding capacity. In conclusion, only the membrane-anchored form of CX3CL1 functionally discriminated between these two allelic isoforms of CX3CR1. These results suggest that each form of this ligand may lead to a different signaling pathway. The extra adhesion of CX3CR1-IM may be related to immune defenses and to atherogenesis, both of which depend substantially on adhesive intercellular events.

Cross-linking of the beta-glucan receptor on human monocytes results in interleukin-1 receptor antagonist but not interleukin-1 production

Blood ◽  
1993 ◽  
Vol 82 (12) ◽  
pp. 3695-3700 ◽  
Author(s):  
DD Poutsiaka ◽  
M Mengozzi ◽  
E Vannier ◽  
B Sinha ◽  
CA Dinarello
Keyword(s):  
Receptor Antagonist ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Interleukin 1 ◽  
Beta Glucan ◽  
Peripheral Blood Mononuclear ◽  
Naturally Occurring ◽  
Beta Glucans ◽  
Or Gene ◽  
Plastic Surfaces

Abstract The beta-glucan receptor, found on monocytes and neutrophils, binds glucose polymers derived from fungi. Ligands for the receptor have various immunomodulatory effects, including increased microbicidal killing activity. We have investigated the effect of beta-glucans on the production of interleukin-1 (IL-1) and its naturally occurring inhibitor, the IL-1 receptor antagonist (IL-1Ra). Particulate beta- glucan induced IL-1Ra production from human peripheral blood mononuclear cells (PBMC) but did not stimulate IL-1 beta synthesis or gene expression in these same cells. Monomeric (soluble) beta-glucan did not induce IL-1Ra production. However, when preincubated with PBMC, monomeric beta-glucan significantly (P <.01) reduced particulate beta- glucan induction of IL-1Ra by 40%, suggesting that crosslinking of beta- glucan receptors is required for induction of IL-1Ra. In support of this, monomeric beta-glucan immobilized on plastic surfaces stimulated IL-1Ra production. Vitamin D3, which increases the functional capacity of beta-glucan receptors, increased IL-1Ra production induced by particulate beta-glucan, whereas dexamethasone suppressed IL-1Ra synthesis. Because of their differential effects on cytokine production, beta-glucans may be used to therapeutic advantage in the diseases in which IL-1 is implicated.

scholarly journals HIV-1 Variation Diminishes CD4 T Lymphocyte Recognition

1998 ◽  
Vol 188 (10) ◽  
pp. 1785-1793 ◽  
Author(s):  
Gillian C. Harcourt ◽  
Sarah Garrard ◽  
Miles P. Davenport ◽  
Anne Edwards ◽  
Rodney E. Phillips
Keyword(s):  
T Lymphocyte ◽  
Mononuclear Cells ◽  
Antigenic Variation ◽  
Class Ii ◽  
Hla Class Ii ◽  
Peripheral Blood Mononuclear ◽  
Altered Peptide Ligands ◽  
Peptide Epitopes ◽  
Naturally Occurring ◽  
Hiv 1

Effective long-term antiviral immunity requires specific cytotoxic T lymphocytes and CD4+ T lymphocyte help. Failure of these helper responses can be a principle cause of viral persistence. We sought evidence that variation in HIV-1 CD4+ T helper epitopes might contribute to this phenomenon. To determine this, we assayed fresh peripheral blood mononuclear cells from 43 asymptomatic HIV-1+ patients for proliferative responses to HIV-1 antigens. 12 (28%) showed a positive response, and we went on to map dominant epitopes in two individuals, to p24 Gag restricted by human histocompatibility leukocyte antigen (HLA)-DR1 and to p17 Gag restricted by HLA-DRB52c. Nine naturally occurring variants of the p24 Gag epitope were found in the proviral DNA of the individual in whom this response was detected. All variants bound to HLA-DR1, but three of these peptides failed to stimulate a CD4+ T lymphocyte line which recognized the index sequence. Antigenic variation was also detected in the p17 Gag epitope; a dominant viral variant present in the patient was well recognized by a specific CD4+ T lymphocyte line, whereas several natural mutants were not. Importantly, variants detected at both epitopes also failed to stimulate fresh uncultured cells while index peptide stimulated successfully. These results demonstrate that variant antigens arise in HIV-1+ patients which fail to stimulate the T cell antigen receptor of HLA class II–restricted lymphocytes, although the peptide epitopes are capable of being presented on the cell surface. In HIV-1 infection, naturally occurring HLA class II–restricted altered peptide ligands that fail to stimulate the circulating T lymphocyte repertoire may curtail helper responses at sites where variant viruses predominate.

scholarly journals Interleukin-15 Triggers the Proliferation and Cytotoxicity of Granular Lymphocytes in Patients With Lymphoproliferative Disease of Granular Lymphocytes

Blood ◽  
1997 ◽  
Vol 89 (1) ◽  
pp. 201-211 ◽  
Author(s):  
R. Zambello ◽  
M. Facco ◽  
L. Trentin ◽  
R. Sancetta ◽  
C. Tassinari ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Lymphoproliferative Disease ◽  
Pcr Analysis ◽  
Rt Pcr ◽  
Peripheral Blood Mononuclear ◽  
Functional Activities ◽  
Clear Cut ◽  
Membrane Bound ◽  
Interleukin 15 ◽  
Granular Lymphocytes

Abstract The recently cloned cytokine interleukin-15 (IL-15) shares several functional activities with IL-2 in different cell systems. Although IL-15 does not show sequence homology with IL-2, it uses components of the IL-2 receptor (IL-2R) for binding and signal transduction, namely, p75 (β) and the p64 (γ) chains of IL-2R. To evaluate whether IL-15 is involved in the activation of granular lymphocytes (GL) in patients with lymphoproliferative disease of granular lymphocytes (LDGL), we evaluated the ability of IL-15 to stimulate GL proliferation, cytotoxic function, and the role of IL-2R β and γ molecules on relevant cells. Our results show that IL-15 stimulates cell proliferation and cytotoxic activity of GL in LDGL patients. Reverse-transcriptase polymerase chain reaction (RT-PCR) and phenotypic analyses using the anti–IL-2R γ-chain–specific TUGh4 monoclonal antibody (MoAb) indicate that both CD3+ and CD3− GL express the p64 IL-2R, a result previously unknown. IL-15 activity was inhibited by antibodies against p75 and p64 IL-2R chains, while no inhibitory effects are detectable with anti-p55 IL-2R antibody. The association of anti-p75 and anti-p64 IL-2R MoAbs resulted in a nearly complete (95%) inhibition of IL-15–induced GL proliferation. Using RT-PCR analysis, we demonstrated that highly purified CD3+ and CD3− GL did not express mRNA for IL-15 or IL-2. By contrast, a clear-cut IL-15 mRNA signal was detected by RT-PCR in patients' peripheral blood mononuclear cells, with monocytes likely accounting for the source of IL-15 in LDGL patients. However, even in concentrated supernatants from enriched monocyte populations, we could not demonstrate the presence of IL-15 protein. Using anti–IL-15 specific MoAbs, a membrane-bound form of this cytokine was demonstrated both on CD3+ and CD3− LDGL cells. By RT-PCR analysis, purified GL from these patients were found to express the message for IL-15 receptor α chain. Taken together, these results indicate that both CD3+ and CD3− GL are stimulated by IL-15 and that this cytokine mediates its activity through the β and γ chains of the IL-2R, providing further suggestions for the interpretation of the mechanisms that lead to cell expansion in patients with LDGL.

Cardiopulmonary Bypass Decreases G Protein–Coupled Receptor Kinase Activity and Expression in Human Peripheral Blood Mononuclear Cells

2003 ◽  
Vol 98 (2) ◽  
pp. 343-348 ◽  
Author(s):  
Scott A. Hagen ◽  
Amy L. Kondyra ◽  
Hilary P. Grocott ◽  
Habib El-Moalem ◽  
Daniel Bainbridge ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
G Protein ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
G Protein Coupled Receptor ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
G Protein Coupled

Background Cardiopulmonary bypass (CPB) has been implicated in the development of organ injury associated with cardiac surgery. At the molecular level, CPB is accompanied by a pronounced proinflammatory response including an increase in plasma interleukin (IL)-6. The IL-6 has been shown to be increased in rheumatoid arthritis, a chronic inflammatory disease, where it has been implicated in decreasing G protein-coupled receptor kinases (GRKs) in peripheral blood mononuclear cells. Since IL-6 is substantially increased after CPB, the study tested whether the increase of IL-6 during CPB leads to a decrease of GRKs in mononuclear cells. This is important because GRKs regulate the function of G protein-coupled receptors involved in inflammation. Methods Fifteen patients had blood withdrawn before CPB, 2 h after CPB, and on postoperative day one (POD1). Plasma IL-6 concentrations were determined by enzyme-linked immunosorbent assay. The GRK protein expression and activity were determined by Western blot and phosphorylation of rhodopsin using [gamma-(32)P] adenosine triphosphate, respectively. Results Plasma IL-6 increased over 20-fold after CPB and remained increased on POD1. Cytosolic GRK activity in mononuclear cells decreased by 39 +/- 29%; cytosolic GRK2 and membrane-bound GRK6 decreased by 90 +/- 15 and 65 +/- 43%, respectively. The GRK activity and expression of GRK2/GRK6 on POD1 returned to basal levels in many but not all patients. Conclusions The CPB causes a profound decrease in mononuclear cell GRKs, and the recovery of these kinases on POD1 is quite variable. The significance of the variable recovery of GRKs after CPB and their potential role as a marker of clinical outcome deserves further investigation.

Fibronectin modulates expression of interleukin-1 beta and its receptor antagonist in human mononuclear cells

1996 ◽  
Vol 271 (1) ◽  
pp. L61-L69 ◽  
Author(s):  
K. L. Graves ◽  
J. Roman
Keyword(s):  
Receptor Antagonist ◽  
Type I Collagen ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Interleukin 1 ◽  
Type I ◽  
Peripheral Blood Mononuclear ◽  
Human Mononuclear Cells ◽  
Naturally Occurring ◽  
Dose Dependent

Identification of factors that regulate production of proinflammatory cytokines may provide insight into mechanisms governing lung inflammation. One potential regulatory factor highly expressed in inflamed tissues is fibronectin (FN). To determine the potential effects of FN on interleukin (IL)-1 beta production, we exposed human peripheral blood mononuclear cells to soluble FN. This treatment resulted in the accumulation of IL-1 beta mRNA and enhancement of IL-1 beta protein synthesis and secretion. This effect was dose dependent and appeared to be mediated by the integrin alpha 5 beta 1. Treatment with FN also increased production of IL-1 receptor antagonist (IL-1ra), a naturally occurring inhibitor of IL-1 function. However, the stimulatory effect of FN on IL-1ra production was abolished by costimulation with type I collagen. We conclude that the increased deposition of FN in injured tissues may enhance the expression of IL-1 beta mRNA and augment the production and release of IL-1 beta protein by mononuclear cells. Differential expression of IL-1 beta and IL-1ra resulting in a high IL-1 beta-to-IL-1ra ratio in response to mixed matrices containing FN and type I collagen may be an important regulatory point in inflammation.

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