Biomedical subjects

Laura Maggi

Publications and source records attributed to Laura Maggi.

4 recordsLinked to original sources

PubMed2005

CD14+CD34low cells with stem cell phenotypic and functional features are the major source of circulating endothelial progenitors.

Endothelial progenitor cells (EPCs) seem to be a promising tool for cell therapy of acute myocardial infarction, but their nature is still unclear. We show here that EPCs obtainable from peripheral blood (PB) derive from the adhesion-related selection in culture of a subset of CD14+ cells, which, when assessed by the highly-sensitive antibody-conjugated magnetofluorescent liposomes (ACMFL) technique, were found to express CD34. These CD14+CD34low cells represented a variable proportion at individual level of CD14+ cells, ranging from 0.6% to 8.5% of all peripheral-blood leukocytes, and constituted the dominant population among circulating KDR+ cells. By using the ACMFL technique, virtually all CD14+ cells present in the bone marrow were found to be CD14+CD34low double-positive cells. EPCs, as well as purified circulating CD14+CD34low cells, exhibited high expression of embryonic stem cell (SC) markers Nanog and Oct-4, which were downregulated in a STAT3-independent manner when they differentiated into endothelial cells (ECs). Moreover, circulating CD14+CD34low cells, but not CD14+CD34- cells, proliferated in response to SC growth factors, and exhibited clonogenicity and multipotency, as shown by their ability to differentiate not only into ECs, but also into osteoblasts, adipocytes, or neural cells. The results of this study may reconcile apparently contradictory data of the literature, showing the generation of PB-derived EPCs from either CD34+ or CD14+ cells. We suggest that the use of this previously unrecognized population of circulating CD14+CD34low cells, which exhibit both phenotypic and functional features of SCs, may be useful in improving cell-based therapies of vascular and tissue damage.

Antigens, CD↗

PubMed2005

CXCR3-mediated opposite effects of CXCL10 and CXCL4 on TH1 or TH2 cytokine production.

BACKGROUND: Two variants of the CXCR3 receptor exist, one (CXCR3-A) reactive with CXCL9, CXCL10, and CXCL11 and the other (CXCR3-B) also reactive with CXCL4. Both variants are contemporarily expressed by human T cells. OBJECTIVE: We sought to investigate the in vitro effects of CXCL10 and CXCL4 on the production of TH1 or TH2 cytokines. METHODS: The cytokine profile of antigen-specific human CD4+ T-cell lines obtained in the absence or presence of CXCL10 or CXCL4 was evaluated by means of quantitative RT-PCR, flow cytometry, and ELISA. RESULTS: CXCL10 upregulated IFN-gamma and downregulated IL-4, IL-5, and IL-13 production, whereas CXCL4 downregulated IFN-gamma and upregulated TH2 cytokines. Similar effects were also observed on polyclonally activated pure naive CD4+ T cells. The opposite effects of CXCL10 and CXCL4 on TH1 and TH2 cytokine production were inhibited by an anti-CXCR3 antibody able to neutralize both CXCR3-A and CXCR3-B and were apparently related to the activation of distinct signal transduction pathways. Moreover, CXCL10 upregulated mRNA levels of T-box expressed in T cells and downregulated GATA-3 expression, whereas CXCL4 downregulated T-box expressed in T cells and upregulated GATA-3. Finally, CXCL4, but not CXCL10, induced direct activation of IL-5 and IL-13 promoters. CONCLUSION: CXCL10 and CXCL4 exert opposite effects on the production of human TH1 and TH2 cytokines, likely through their respective interaction with CXCR3-A or CXCR3-B and the consequent activation of different signal transduction pathways. This might represent an internal regulatory pathway of TH cell responses and might contribute to the modulation of chronic inflammatory reactions, including allergy.

CD4-Positive T-Lymphocytes↗

PubMed2004

Persistent decrease in synaptic efficacy induced by nicotine at Schaffer collateral-CA1 synapses in the immature rat hippocampus.

Neuronal nicotinic acetylcholine receptors (nAChRs) are widely distributed within the brain where they contribute to the regulation of higher cognitive functions. The loss of the cholinergic function in Alzheimer's disease patients, along with the well-known memory enhancing effect of nicotine, emphasizes the role of cholinergic signalling in memory functions. The hippocampus, a key structure in learning and memory, is endowed with nAChRs localized at pre- and postsynaptic levels. In previous work on the immature hippocampus we have shown that, at low probability (P) synapses, activation of alpha7 nAChRs by nicotine or by endogenously released acetylcholine persistently enhanced glutamate release and converted 'presynaptically silent' synapses into functional ones. Here we show that in the same preparation, at high P synapses, nicotine induces long-term depression of AMPA- and NMDA-mediated synaptic currents. This effect was mediated by presynaptic alpha7- and beta2-containing receptors and was associated with an increase in the paired pulse ratio and in the coefficient of variation. High P synapses could be converted into low P and vice versa by changing the extracellular Ca2+/Mg2+ ratio. In these conditions nicotine was able to persistently potentiate or depress synaptic responses depending on the initial P-values. A bi-directional control of synaptic plasticity by nicotine would considerably enhance the computational properties of the network during a critical period of postnatal development thus contributing to sculpt the neuronal circuit.

Animals↗

PubMed2003

Nicotine activates immature "silent" connections in the developing hippocampus.

In the hippocampus at birth, most glutamatergic synapses are immature and functionally "silent" either because the neurotransmitter is released in insufficient amount to activate low-affinity alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors or because the appropriate receptor system is missing or nonfunctional. Here we show that, in the newborn rat, a brief application of nicotine at immature Schaffer collateral-CA1 connections strongly enhances neurotransmitter release and converts presynaptically silent synapses into conductive ones. This effect is persistent and can be mimicked by endogenous acetylcholine released from cholinergic fibers. Thus, during a critical period of postnatal development, activation of nicotinic acetylcholine receptors contributes to the maturation of functional synaptic contacts and the wiring of adult hippocampal circuitry.

Acetylcholine↗