No abstract

Macrophages are key in orchestrating immune responses to micro-environmental stimuli, sensed by a complex set of surface receptors. The human cell line THP-1 has a monocytic phenotype, including the ability to differentiate into macrophages, providing a tractable, standardised surrogate for human monocyte-derived macrophages. Here we assessed the expression of 49 surface markers including Fc, complement, C-type lectin and scavenger receptors; TIMs; Siglecs; and co-stimulatory molecules by flow cytometry on both THP-1 monocytes and macrophages and following macrophage activation with seven standard conditioning/polarizing stimuli. Of the 34 surface markers detected on macrophages, 18 altered expression levels on activation. From these, expression of 9 surface markers were consistently altered by all conditioning regimens, while 9 were specific to individual polarizing stimuli. This study provides a resource for the study of macrophages and highlights that macrophage polarization states share much in common and the differences do not easily fit a simple classification system.

The Ceprano calvarium represents one of the most important sources of information about both the dynamics of the earliest hominid dispersal toward Europe and the evolution of the genus Homo in the early‐to‐middle Pleistocene. In this paper, the midsagittal vault profile and the 3D frontal bone morphology of Ceprano are investigated comparatively, using landmark coordinates and Procrustes superimposition. In fact, despite the fact that the skull appears partially distorted by diagenetic pressures (thus precluding a comprehensive landmark‐based analysis), some aspects of the overall morphology are suitable for consideration in terms of geometric morphometrics. The midsagittal profile shows an archaic shape, comparable with the H. ergaster/erectus range of variation because of the fronto‐parietal flattening, the development of the supraorbital and nuchal structures, and the occurrence of a slightly larger occipital bone. By contrast, the frontal bone displays a derived 3D shape that, mostly because of the widening of the frontal squama, appears comparable with the Afro‐European variation of the Middle Pleistocene (i.e., H. heidelbergensis/rhodesiensis). Taking into account the unique morphological pattern displayed by Ceprano, its role as a link between early Homo and the Middle Pleistocene populations of Europe and Africa is not falsified. Thus, when aspects of the Ceprano's morphology are described within the analytical framework provided by geometric morphometrics, the relationships between Ceprano and the subsequent Afro‐European fossil record are emphasized, suggesting the occurrence of an ancestral stock of H. heidelbergensis/rhodesiensis that is properly represented by the Italian specimen. Am J Phys Anthropol, 2007. © 2006 Wiley‐Liss, Inc.

No abstract

In both sickle cell disease and malaria, red blood cells (RBCs) are phagocytosed in the spleen, but receptor-ligand pairs mediating uptake have not been identified. Here, we report that patches of high mannose N-glycans (Man5-9GlcNAc2), expressed on diseased or oxidized RBC surfaces, bind the mannose receptor (CD206) on phagocytes to mediate clearance. We find that extravascular hemolysis in sickle cell disease correlates with high mannose glycan levels on RBCs. Furthermore, Plasmodium falciparum-infected RBCs expose surface mannose N-glycans, which occur at significantly higher levels on infected RBCs from sickle cell trait subjects compared to those lacking hemoglobin S. The glycans are associated with high molecular weight complexes and protease-resistant, lower molecular weight fragments containing spectrin. Recognition of surface N-linked high mannose glycans as a response to cellular stress is a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait.