The obesity and inflammatory marker haptoglobin attracts monocytes via interaction with chemokine (C-C motif) receptor 2 (CCR2)

Margherita Maffei , Marcella Funicello , Teresa Vottari , Olimpia Gamucci , Mario Costa , Simonetta Lisi , Alessandro Viegi , Osele Ciampi , Giuseppe Bardi , Paolo Vitti , Aldo Pinchera and Ferruccio Santini

BMC Biology 2009, 7:87doi:10.1186/1741-7007-7-87


Published:	17 December 2009

Abstract (provisional)

Background

Obesity is a chronic low inflammatory state. In the obesity condition the white adipose tissue (WAT) is massively infiltrated with monocytes/macrophages, and the nature of the signals recruiting these inflammatory cells has yet to be fully elucidated. Haptoglobin (Hp) is an inflammatory marker and its expression is induced in the WAT of obese subjects. In an effort to elucidate the biological significance of Hp presence in the WAT and of its upregulation in obesity we formulated the hypothesis that Hp may serve as a macrophage chemoattractant.

Results

We demonstrated by chemotaxis assay that Hp is able to attract chemokine (C-C motif) receptor 2 (CCR2)-transfected pre-B lymphocytes and monocytes in a dose-dependent manner. Moreover, Hp-mediated migration of monocytes is impaired by CCR2-specific inhibition or previous cell exposure to monocyte chemoattractant protein 1 (MCP1) (also known as CCR2 ligand or chemokine (C-C motif) ligand 2 (CCL2)). Downstream effects of Hp/CCR2 interaction were also investigated: flow cytometry proved that monocytes treated with Hp show reduced CCR2 expression on their surface; Hp interaction induces calcium release that is reduced upon pretreatment with CCR2 antagonist; extracellular signal-regulated kinase (ERK)1/2, a signal transducer activated by CCR2, is phosphorylated following Hp treatment and this phosphorylation is reduced when cells are pretreated with a specific CCR2 inhibitor. Consistently, blocking the ERK1/2 pathway with U0126, the selective inhibitor of the ERK upstream mitogen-activated protein (MAP)-ERK kinase (MEK), results in a dramatic reduction (by almost 100%) of the capability of Hp to induce monocyte migration.

Conclusions

Our data show that Hp is a novel monocyte chemoattractant and that its chemotactic potential is mediated, at least in part, by its interaction with CCR2.

Revolution of novel fungal genes

The evolution of novel fungal genes from non-retroviral RNA viruses

Derek J. Taylor and Jeremy Bruenn

BMC Biology 2009, 7:88doi:10.1186/1741-7007-7-88


Published:	18 December 2009

Abstract (provisional)

Background

Endogenous derivatives of non-retroviral RNA viruses are thought to be absent or rare in eukaryotic genomes because integration of RNA viruses in host genomes is impossible without reverse transcription. However, such derivatives have been proposed for animals, plants and fungi, often based on surrogate bioinformatic evidence. At present, there is little known of the evolution and function of integrated non-retroviral RNA virus genes. Here, we provide direct evidence of integration by sequencing across host-virus gene boundaries and carry out phylogenetic analyses of fungal hosts and totivirids (dsRNA viruses of fungi and protozoans). Further, we examine functionality by tests of neutral evolution, comparison of residues that are necessary for viral capsid functioning and assays for transcripts, dsRNA and viral particles.

Results

Sequencing evidence from gene boundaries was consistent with integration. We detected previously unknown integrated Totivirus-like sequences in three fungi (Candida parapsilosis, Penicillium marneffei and Uromyces appendiculatus). The phylogenetic evidence strongly indicated that the direction of transfer was from Totivirus to fungus. However, there was evidence of transfer of Totivirus-like sequences among fungi. Tests of selection indicated that integrated genes are maintained by purifying selection. Transcripts were apparent for some gene copies, but, in most cases, the endogenous sequences lacked the residues necessary for normal viral functioning.

Conclusions

Our findings reveal that horizontal gene transfer can result in novel gene formation in eukaryotes despite miniaturized genomic targets and a need for co-option of reverse transcriptase.