Clearance of apoptotic cells by macrophages induces regulatory phenotype and involves stimulation of cd36 and platelet-activating factor receptor

Phagocytosis of apoptotic cells (efferocytosis) induces macrophage differentiation towards a regulatory phenotype (IL-10high/IL-12p40low). CD36 is involved in the recognition of apoptotic cells (AC), and we have shown that the platelet-activating factor receptor (PAFR) is also involved. Here, we investigated the contribution of PAFR and CD36 to efferocytosis and to the establishment of a regulatory macrophage phenotype. Mice bone marrow-derived macrophages were cocultured with apoptotic thymocytes, and the phagocytic index was determined. Blockage of PAFR with antagonists or CD36 with specific antibodies inhibited the phagocytosis of AC (~70–80%). Using immunoprecipitation and confocal microscopy, we showed that efferocytosis increased the CD36 and PAFR colocalisation in the macrophage plasma membrane; PAFR and CD36 coimmunoprecipitated with flotillin-1, a constitutive lipid raft protein, and disruption of these membrane microdomains by methyl-β-cyclodextrin reduced AC phagocytosis. Efferocytosis induced a pattern of cytokine production, IL-10high/IL-12p40low, that is, characteristic of a regulatory phenotype. LPS potentiated the efferocytosis-induced production of IL-10, and this was prevented by blocking PAFR or CD36. It can be concluded that phagocytosis of apoptotic cells engages CD36 and PAFR, possibly in lipid rafts, and this is required for optimal efferocytosis and the establishment of the macrophage regulatory phenotype

Singularities of affine equidistants: projections and contacts

Using standard methods for studying singularities of projections and of contacts, we classify the stable singularities of affine $\lambda$-equidistants of $n$-dimensional closed submanifolds of $\mathbb R^q$, for $q\leq 2n$, whenever $(2n,q)$ is a pair of nice dimensions.Comment: 18 pages, v2 (minimal changes) agrees with version to appear in Journal of Singularitie

Multi-layer model for the web graph

This paper studies stochastic graph models of the WebGraph. We present a new model that describes the WebGraph as an ensemble of different regions generated by independent stochastic processes (in the spirit of a recent paper by Dill et al. [VLDB 2001]). Models such as the Copying Model [17] and Evolving Networks Model [3] are simulated and compared on several relevant measures such as degree and clique distribution

Develop an MEP Based Scheduling Learning Module with Industry Support and Guidance to Understand the Impact on the General Contractor

The Construction Management (CM) program at Cal Poly, San Luis Obispo is recognized as one of the best construction programs in country. The curriculum does an extraordinary job at teaching how to utilize software and technology to create a project schedule. The one thing that the curriculum lacks is learning sequencing of events when it comes to scheduling, and where to look to obtain this information. Although learning sequencing for scheduling is hard to teach because it comes with years of industry experience, it is important to have a basic understanding of how things come together to create a functioning project schedule. A way to understand sequencing is by learning a about the design of the systems that the general contractor is installing. By learning what the engineers do, it allows for the general contractor to understand how much time is going to be needed to install the required systems. As a general contractor it is important to bring on your MEP subcontractors early on because the MEP trades make up a great chunk of their overall budget. This learning module will not only help understand sequencing for general schedules, it will also make students more aware of the impact specialty contractors have on the general contractor

Oxidized LDL induces alternative macrophage phenotype through activation of CD36 and PAFR

OxLDL is recognized by macrophage scavenger receptors, including CD36; we have recently found that Platelet-Activating Factor Receptor (PAFR) is also involved. Since PAFR in macrophages is associated with suppressor function, we examined the effect of oxLDL on macrophage phenotype. It was found that the presence of oxLDL during macrophage differentiation induced high mRNA levels to IL-10, mannose receptor, PPARγ and arginase-1 and low levels of IL-12 and iNOS. When human THP-1 macrophages were pre-treated with oxLDL then stimulated with LPS, the production of IL-10 and TGF-β significantly increased, whereas that of IL-6 and IL-8 decreased. In murine TG-elicited macrophages, this protocol significantly reduced NO, iNOS and COX2 expression. Thus, oxLDL induced macrophage differentiation and activation towards the alternatively activated M2-phenotype. In murine macrophages, oxLDL induced TGF-β, arginase-1 and IL-10 mRNA expression, which were significantly reduced by pre-treatment with PAFR antagonists (WEB and CV) or with antibodies to CD36. The mRNA expression of IL-12, RANTES and CXCL2 were not affected. We showed that this profile of macrophage activation is dependent on the engagement of both CD36 and PAFR. We conclude that oxLDL induces alternative macrophage activation by mechanisms involving CD36 and PAFR

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