Social inequalities in male mortality, and in male mortality from smoking: indirect estimation from national death rates in England and Wales, Poland, and North America

Background There are substantial social inequalities in adult male mortality in many countries. Smoking is often more prevalent among men of lower social class, education, or income. The contribution of smoking to these social inequalities in mortality remains uncertain. Methods The contribution of smoking to adult mortality in a population can be estimated indirectly from disease-specific death rates in that population (using absolute lung cancer rates to indicate proportions due to smoking of mortality from certain other diseases). We applied these methods to 1996 death rates at ages 35-69 years in men in three different social strata in four countries, based on a total of 0.6 million deaths. The highest and lowest social strata were based on social class (professional vs unskilled manual) in England and Wales, neighbourhood income (top vs bottom quintile) in urban Canada, and completed years of education (more than vs less than 12 years) in the USA and Poland. Results In each country, there was about a two-fold difference between the highest and the lowest social strata in overall risks of dying among men aged 35-69 years (England and Wales 21% vs 43%, USA 20% vs 37%, Canada 21% vs 34%, Poland 26% vs 50%: four-country mean 22% vs 41%, four-country mean absolute difference 19%). More than half of this difference in mortality between the top and bottom social strata involved differences in risks of being killed at age 35-69 years by smoking (England and Wales 4% vs 19%, USA 4% vs 15%, Canada 6% vs 13%, Poland 5% vs 22%: four-country mean 5% vs 17%, four-country mean absolute difference 12%). Smoking-attributed mortality accounted for nearly half of total male mortality in the lowest social stratum of each country. Conclusion In these populations, most, but not all, of the substantial social inequalities in adult male mortality during the 1990s were due to the effects of smoking. Widespread cessation of smoking could eventually halve the absolute differences between these social strata in the risk of premature death.

Corpos mortos e vivos: as cerimônias mortuárias e as representações da morte entre católicos brasileiros

Esta pesquisa procurou descrever, analisar e comparar as cerimônias mortuárias e as representações coletivas de católicos brasileiros da morte e do luto. Tivemos por objetivo estudar os sistemas simbólicos desenvolvidos em várias sociedades, começando com as culturas tribais, passando depois para o cristianismo dos primeiros séculos, antes da instauração do processo de institucionalização que originou o cristianismo católico e durante ele. Analisamos as práticas e representações católicas relacionadas com a morte e o morrer, na Idade Média, Idade Moderna e Contemporânea, tanto na Europa como no Brasil. O objetivo também foi apresentar os ritos mortuários como formas de dar sentido à vida, de reforçar e manter a coesão social, em que indivíduos vivem constantemente os desarranjos gerados pela presença da morte que arrebata um dos seus semelhantes provocando um desequilíbrio social. Ao realizar tal pesquisa sobre os rituais mortuários católicos, a meta consistiu em avançar um pouco mais no conhecimento sobre um fenômeno social religioso nem sempre abordado pelos pesquisadores: a morte do crente, as práticas mortuárias dos grupos católicos, seus hábitos e discurso quanto ao morto, dentro de um cenário brasileiro que se torna cada vez mais urbano e secularizado.(AU)

Corpos Enlutados: Por um cuidado espiritual terapêutico em situações de luto

Esta tese tem como objetivo compreender o fenômeno do luto por morte a partir da fenomenologia, por meio das experiências de membros da Igreja Metodista no Grande ABC. Para alcançar o objetivo geral, tem como objetivos específicos: dialogar com teóricos do luto nas áreas da teologia e da psicologia; conhecer a fenomenologia do corpo existencial de Maurice Merleau-Ponty como parâmetro para a compreensão do estudo do luto por morte; contribuir para as pesquisas de Cuidado Espiritual em situações de luto por morte. A trajetória teórico-metodológica tem como lócus da pesquisa o relato oral de dez pessoas, que trazem sua vivência do luto a partir da pergunta norteadora: como você viveu a sua experiência do luto? Depois de transcritos e literalizados, esses relatos permitiram levantar as unidades de significado e estabelecer as categorias analíticas: dor, tipo de perda, desorganização do ser, corpo existencial, cuidado, fé, luto por morte como ordem natural, processo relacional, racionalização, saudade, luto antecipatório, dimensão material do viver, culpa, memória e serenidade. A partir dessas categorias, fenomenologicamente interpretadas, a construção de uma tabela nomotética tornou possível a identificação das convergências e divergências entre os relatos, bem como das idiossincrasias. No percurso em direção à compreensão da experiência do luto, os relatos foram submetidos à análise ideográfica, que é a tentativa de alcançar a psicologia individual dos sujeitos da pesquisa. A síntese de um pensar, como a expressão da fenomenologia do luto, desvela nuanças da práxis pastoral. Resultantes da construção desse novo saber em torno da vivência do luto por morte, foram significativas algumas percepções: o processo do luto no contexto religioso institucionalizado é similar ao de um contexto não-religioso; a teologia cristã tem espaço para a ressignificação da morte, por meio da criação de uma espiritualidade para o processo do morrer e, para que isso seja possível, destaca-se a necessidade, no interior das comunidades religiosas, de uma teologia da perda, que possibilite uma educação cristã voltada para o enfrentamento do luto, ou seja, de uma teologia de valorização da vida em meio às perdas; o corpo foi a linguagem mais presente na vivência do luto e, no entanto, o corpo enlutado é um paradoxo na igreja cristã, na medida em que esta se tem debruçado sobre o tema da corpo de forma tímida, no que se refere à educação da fé. Ficou patente a percepção da necessidade de fomentar um cuidado espiritual terapêutico abrangente e continuado em situações de luto, de forma a alcançar não apenas o indivíduo em situação de enlutamento, mas também de alcance comunitário, como parte do conjunto de ações públicas que acolham essa questão.(AU)

The role of the innate immune system in the clearance of apoptotic cells

Rapid clearance of dying cells is a vital feature of apoptosis throughout development, tissue homeostasis and resolution of inflammation. The phagocytic removal of apoptotic cells is mediated by both professional and amateur phagocytes, armed with a series of pattern recognition receptors that participate in host defence and apoptotic cell clearance. CD14 is one such molecule. It is involved in apoptotic cell clearance (known to be immunosuppressive and anti-inflammatory) and binding of the pathogen-associated molecular pattern, lipopolysaccharides (a pro-inflammatory event). Thus CD14 is involved in the assembly of two distinct ligand-dependent macrophage responses. This project sought to characterise the involvement of the innate immune system, particularly CD14, in the removal of apoptotic cells. The role of non-myeloid CD14 was also considered and the data suggests that the expression of CD14 by phagocytes may define their professional status as phagocytes. To assess if differential CD14 ligation causes the ligand-dependent divergence in macrophage responses, a series of CD14 point mutants were used to map the binding of apoptotic cells and lipopolysaccharides. Monoclonal antibodies, 61D3 and MEM18, known to interfere with ligand-binding and responses, were also mapped. Data suggests that residue 11 of CD14, is key for the binding of 61D3 (but not MEM18), LPS and apoptotic cells, indicating lipopolysaccharides and apoptotic cells bind to similar residues. Furthermore using an NF-kB reporter, results show lipopolysaccharides but not apoptotic cells stimulate NF-kB. Taken together these data suggests ligand-dependent CD14 responses occur via a mechanism that occurs downstream of CD14 ligation but upstream of NF-?B activation. Alternatively apoptotic cell ligation of CD14 may not result in any signalling event, possibly by exclusion of TLR-4, suggesting that engulfment receptors, (e.g. TIM-4, BAI1 and Stablin-2) are required to mediate the uptake of apoptotic cells and the associated anti-inflammatory response.

Modelling Apoptotic cell clearance within the atherosclerotic plaque

The aged population have an increased susceptibility to infection, therefore function of the innate immune system may be impaired as we age. Macrophages, and their precursors monocytes, play an important role in host defence in the form of phagocytosis, and also link the innate and adaptive immune system via antigen presentation. Classically-activated 'M1' macrophages are pro-inflammatory, which can be induced by encountering pathogenic material or pro-inflammatory mediators. Alternatively activated 'M2' macrophages have a largely reparative role, including clearance of apoptotic bodies and debris from tissues. Despite some innate immune receptors being implicated in the clearance of apoptotic cells, the process has been observed to have a dominant anti-inflammatory phenotype with cytokines such as IL-10 and TGF-ß being implicated. The atherosclerotic plaque contains recruited monocytes and macrophages, and is a highly inflammatory environment despite high levels of apoptosis. At these sites, monocytes differentiate into macrophages and gorge on lipoproteins, resulting in formation of 'foam cells' which then undergo apoptosis, recruiting further monocytes. This project seeks to understand why, given high levels of apoptosis, the plaque is a pro-inflammatory environment. This phenomenon may be the result of the aged environment or an inability of foam cells to elicit an anti-inflammatory effect in response to dying cells. Here we demonstrate that lipoprotein treatment of macrophages in culture results in reduced capacity to clear apoptotic cells. The effect of lipoprotein treatment on apoptotic cell-mediated immune modulation of macrophage function is currently under study.

Importance of tissue transglutaminase in repair of extracellular matrices and cell death of dermal fibroblasts after exposure to a solarium ultraviolet A source

Investigations were undertaken to study the role of the protein cross-linking enzyme tissue transglutaminase in changes associated with the extracellular matrix and in the cell death of human dermal fibroblasts following exposure to a solarium ultraviolet A source consisting of 98.8% ultraviolet A and 1.2% ultraviolet B. Exposure to nonlethal ultraviolet doses of 60 to 120 kJ per m2 resulted in increased tissue transglutaminase activity when measured either in cell homogenates, "in situ" by incorporation of fluorescein-cadaverine into the extracellular matrix or by changes in the epsilon(gamma-glutamyl) lysine cross-link. This increase in enzyme activity did not require de novo protein synthesis. Incorporation of fluorescein-cadaverine into matrix proteins was accompanied by the cross-linking of fibronectin and tissue transglutaminase into nonreducible high molecular weight polymers. Addition of exogenous tissue transglutaminase to cultured cells mimicking extensive cell leakage of the enzyme resulted in increased extracellular matrix deposition and a decreased rate of matrix turnover. Exposure of cells to 180 kJ per m2 resulted in 40% to 50% cell death with dying cells showing extensive tissue transglutaminase cross-linking of intracellular proteins and increased cross-linking of the surrounding extracellular matrix, the latter probably occurring as a result of cell leakage of tissue transglutaminase. These cells demonstrated negligible caspase activation and DNA fragmentation but maintained their cell morphology. In contrast, exposure of cells to 240 kJ per m2 resulted in increased cell death with caspase activation and some DNA fragmentation. These cells could be partially rescued from death by addition of caspase inhibitors. These data suggest that changes in cross-linking both in the intracellular and extracellular compartments elicited by tissue transglutaminase following exposure to ultraviolet provides a rapid tissue stabilization process following damage, but as such may be a contributory factor to the scarring process that results.

Apoptotic cell‐associated ICAM‐3 in the phagocytic removal of apoptotic cells

Apoptosis is a highly controlled cell death programme that culminates in the exposure of molecular ‘flags’ at the dying cell surface that permit recognition and removal by viable phagocytes. Failure to efficiently remove dying cells can lead to devastating inflammatory and autoimmune disorders. The molecular mechanisms underlying apoptotic cell surface changes are poorly understood. Our previous work has shown an apoptosis-associated functional change in ICAM-3 (a heavily glycosylated, leukocyte-restricted Immunoglobulin Super-Family member) resulting in a molecular ‘flag’ to mediate corpse removal. Here we detail apoptosis-associated changes in ICAM-3 and define their role in ICAM-3’s novel function in apoptotic cell clearance. We show ICAM-3 functions to tether apoptotic leukocytes to macrophages via an undefined receptor. Though CD14 has been suggested as a possible receptor for apoptotic cell-associated ICAM-3, we demonstrate ICAM-3 functions for apoptotic cell clearance in the absence of CD14. Furthermore, we demonstrate leukocytes display early changes in cell surface glycosylation and a marked reduction in ICAM-3, a change that correlates reduced cell volume throughout apoptosis. This loss of ICAM-3 occurs via shedding of ICAM-3 in microparticles (‘apoptotic bodies’). Such microparticles are potent chemoattractants for macrophages. Notably, microparticles from ICAM-3-deficient leukocytes are significantly less chemoattractive than microparticles from their ICAM-3-replete counterparts. These data support the hypothesis that ICAM-3 acts as an apoptotic cell-associated ligand to tether dying cells to phagocytes in a CD14-independent manner. Furthermore our data suggest that released ICAM-3 may promote the recruitment of phagocytes to sites of apoptosis.

Apoptotic cell-derived ICAM-3 promotes both macrophage chemoattraction to and tethering of apoptotic cells

Damaged, aged or unwanted cells are removed from the body by an active process known as apoptosis. This highly orchestrated programme results in cell disassembly and the exposure of ‘flags’ at the dying cell surface that permit recognition and removal by viable cells (phagocytes). Efficient phagocytic removal of dying cells is essential to prevent inflammatory and autoimmune disorders. Relatively little is known of the molecular mechanisms underlying changes at the apoptotic cell surface. We have previously shown that ICAM-3 (a heavily glycosylated, leukocyte-restricted Immunoglobulin Super-Family member) undergoes a change of function as cells die so that it acts as a molecular ‘flag’ to mediate corpse removal. Our work seeks to characterise apoptosis-associated changes in ICAM-3 and define their role in ICAM-3’s novel function in apoptotic cell clearance. Here we extend earlier studies to show that apoptotic cell-associated ICAM-3 functions, at least minimally, to tether apoptotic leukocytes to macrophages via an undefined receptor. Whilst CD14 has been suggested as a possible innate immune receptor for apoptotic cell-associated ICAM-3, we demonstrate ICAM-3 functions for apoptotic cell clearance in the absence of CD14. Our data additionally indicate, that during apoptosis, leukocytes display early changes in cell surface glycosylation and a marked reduction in ICAM-3, a change that correlates with a reduction in cell volume. This reduction in ICAM-3 is explained by cell surface shedding of microparticles (‘apoptotic bodies’) that contain ICAM-3. Such microparticles, released from apoptotic leukocytes, are strongly chemoattractive for macrophages. In addition, microparticles from ICAM-3-deficient leukocytes are significantly less chemoattractive than microparticles from their ICAM-3-replete counterparts. Taken together these data support the hypothesis that ICAM-3 acts as an apoptotic cell-associated ligand to tether dying cells to phagocytes in a CD14-independent manner. Furthermore our data suggest that released ICAM-3 may promote the recruitment of phagocytes to sites of leukocyte apoptosis.

Apoptotic cell-derived ICAM-3 promotes both macrophage chemoattraction to and tethering of apoptotic cells

Damaged, aged or unwanted cells are removed from the body by an active process known as apoptosis. This highly orchestrated programme results in cell disassembly and the exposure of ‘flags’ at the dying cell surface that permit recognition and removal by viable cells (phagocytes). Efficient phagocytic removal of dying cells is essential to prevent inflammatory and autoimmune disorders. Relatively little is known of the molecular mechanisms underlying changes at the apoptotic cell surface. We have previously shown that ICAM-3 (a heavily glycosylated, leukocyte-restricted Immunoglobulin Super-Family member) undergoes a change of function as cells die so that it acts as a molecular ‘flag’ to mediate corpse removal. Our work seeks to characterise apoptosis-associated changes in ICAM-3 and define their role in ICAM-3’s novel function in apoptotic cell clearance. Here we extend earlier studies to show that apoptotic cell-associated ICAM-3 functions, at least minimally, to tether apoptotic leukocytes to macrophages via an undefined receptor. Whilst CD14 has been suggested as a possible innate immune receptor for apoptotic cell-associated ICAM-3, we demonstrate ICAM-3 functions for apoptotic cell clearance in the absence of CD14. Our data additionally indicate, that during apoptosis, leukocytes display early changes in cell surface glycosylation and a marked reduction in ICAM-3, a change that correlates with a reduction in cell volume. This reduction in ICAM-3 is explained by cell surface shedding of microparticles (‘apoptotic bodies’) that contain ICAM-3. Such microparticles, released from apoptotic leukocytes, are strongly chemoattractive for macrophages. In addition, microparticles from ICAM-3-deficient leukocytes are significantly less chemoattractive than microparticles from their ICAM-3-replete counterparts. Taken together these data support the hypothesis that ICAM-3 acts as an apoptotic cell-associated ligand to tether dying cells to phagocytes in a CD14-independent manner. Furthermore our data suggest that released ICAM-3 may promote the recruitment of phagocytes to sites of leukocyte apoptosis.

The innate immune system and the clearance of apoptotic cells

Removal of unwanted, effete, or damaged cells through apoptosis, an active cell death culminating in phagocytic removal of cell corpses, is an important process throughout the immune system in development, control, and homeostasis. For example, neutrophil apoptosis is central to the resolution of acute inflammation, whereas autoreactive and virus-infected cells are similarly deleted. The AC removal process functions not only to remove cell corpses but further, to control inappropriate immune responses so that ACs are removed in an anti-inflammatory manner. Such "silent" clearance is mediated by the innate immune system via polarized monocyte/macrophage populations that use a range of PRRs and soluble molecules to promote binding and phagocytosis of ACs. Additionally, attractive signals are released from dying cells to recruit phagocytes to sites of death. Here, we review the molecular mechanisms associated with innate immune removal of and responses to ACs and outline how these may impact on tissue homeostasis and age-associated pathology (e.g., cardiovascular disease). Furthermore, we discuss how an aging innate immune system may contribute to the inflammatory consequences of aging and why the study of an aging immune system may be a useful path to advance characterization of mechanisms mediating effective AC clearance. © Society for Leukocyte Biology.

Dealing with cell death – an ageing problem?

The aged population have an increased susceptibility to infection, therefore function of the innate immune system may be impaired as we age. Macrophages, and their precursors monocytes, play an important role in host defence in the form of phagocytosis, and also link the innate and adaptive immune system via antigen presentation. Classically-activated ‘M1’ macrophages are pro-inflammatory, which can be induced by encountering pathogenic material or pro-inflammatory mediators. Alternatively activated ‘M2’ macrophages have a largely reparative role, including clearance of apoptotic bodies and debris from tissues. Despite some innate immune receptors being implicated in the clearance of apoptotic cells, the process has been observed to have a dominant anti-inflammatory phenotype with cytokines such as IL-10 and TGF-ß being implicated. The atherosclerotic plaque contains recruited monocytes and macrophages, and is a highly inflammatory environment despite high levels of apoptosis. At these sites, monocytes differentiate into macrophages and gorge on lipoproteins, resulting in formation of ‘foam cells’ which then undergo apoptosis, recruiting further monocytes. This project seeks to understand why, given high levels of apoptosis, the plaque is a pro-inflammatory environment. This phenomenon may be the result of the aged environment or an inability of foam cells to elicit an anti-inflammatory effect in response to dying cells. Here we demonstrate that lipoprotein treatment of macrophages in culture results in reduced capacity to clear apoptotic cells. The capability of lipoprotein treated macrophages to respond to inflammatory stimuli is also shown. Monocyte recruitment to the plaque is currently under study, as is apoptotic cell-mediated immune modulation of human monocyte-derived macrophages.

The N-terminus of CD14 acts to bind apoptotic cells and confers rapid-tethering capabilities on non-myeloid cells:CD14 and rapid tethering of apoptotic cells

Cell death and removal of cell corpses in a timely manner is a key event in both physiological and pathological situations including tissue homeostasis and the resolution of inflammation. Phagocytic clearance of cells dying by apoptosis is a complex sequential process comprising attraction, recognition, tethering, signalling and ultimately phagocytosis and degradation of cell corpses. A wide range of molecules acting as apoptotic cell-associated ligands, phagocyte-associated receptors or soluble bridging molecules have been implicated within this process. The role of myeloid cell CD14 in mediating apoptotic cell interactions with macrophages has long been known though key molecules and residues involved have not been defined. Here we sought to further dissect the function of CD14 in apoptotic cell clearance. A novel panel of THP-1 cell-derived phagocytes was employed to demonstrate that CD14 mediates effective apoptotic cell interactions with macrophages in the absence of detectable TLR4 whilst binding and responsiveness to LPS requires TLR4. Using a targeted series of CD14 point mutants expressed in non-myeloid cells we reveal CD14 residue 11 as key in the binding of apoptotic cells whilst other residues are reported as key for LPS binding. Importantly we note that expression of CD14 in non-myeloid cells confers the ability to bind rapidly to apoptotic cells. Analysis of a panel of epithelial cells reveals that a number naturally express CD14 and that this is competent to mediate apoptotic cell clearance. Taken together these data suggest that CD14 relies on residue 11 for apoptotic cell tethering and it may be an important tethering molecule on so called 'non-professional' phagocytes thus contributing to apoptotic cell clearance in a non-myeloid setting. Furthermore these data establish CD14 as a rapid-acting tethering molecule, expressed in monocytes, which may thus confer responsiveness of circulating monocytes to apoptotic cell derived material. © 2013 Thomas et al.

Innate recognition of apoptotic cells:novel apoptotic cell-associated molecular patterns revealed by crossreactivity of anti-LPS antibodies

Cells dying by apoptosis are normally cleared by phagocytes through mechanisms that can suppress inflammation and immunity. Molecules of the innate immune system, the pattern recognition receptors (PRRs), are able to interact not only with conserved structures on microbes (pathogen-associated molecular patterns, PAMPs) but also with ligands displayed by apoptotic cells. We reasoned that PRRs might therefore interact with structures on apoptotic cells-apoptotic cell-associated molecular patterns (ACAMPs)-that are analogous to PAMPs. Here we show that certain monoclonal antibodies raised against the prototypic PAMP, lipopolysaccharide (LPS), can crossreact with apoptotic cells. We demonstrate that one such antibody interacts with a constitutively expressed intracellular protein, laminin-binding protein, which translocates to the cell surface during apoptosis and can interact with cells expressing the prototypic PRR, mCD14 as well as with CD14-negative cells. Anti-LPS cross reactive epitopes on apoptotic cells colocalised with annexin V-and C1q-binding sites on vesicular regions of apoptotic cell surfaces and were released associated with apoptotic cell-derived microvesicles (MVs). These results confirm that apoptotic cells and microbes can interact with the immune system through common elements and suggest that anti-PAMP antibodies could be used strategically to characterise novel ACAMPs associated not only with apoptotic cells but also with derived MVs. © 2013 Macmillan Publishers Limited All rights reserved.

Current understanding of the mechanisms for clearance of apoptotic cells-a fine balance

Apoptosis is an important cell death mechanism by which multicellular organisms remove unwanted cells. It culminates in a rapid, controlled removal of cell corpses by neighboring or recruited viable cells. Whilst many of the molecular mechanisms that mediate corpse clearance are components of the innate immune system, clearance of apoptotic cells is an anti-inflammatory process. Control of cell death is dependent on competing pro-apoptotic and anti-apoptotic signals. Evidence now suggests a similar balance of competing signals is central to the effective removal of cells, through so called 'eat me' and 'don't eat me' signals. Competing signals are also important for the controlled recruitment of phagocytes to sites of cell death. Consequently recruitment of phagocytes to and from sites of cell death can underlie the resolution or inappropriate propagation of cell death and inflammation. This article highlights our understanding of mechanisms mediating clearance of dying cells and discusses those mechanisms controlling phagocyte migration and how inappropriate control may promote important pathologies. © the authors, publisher and licensee libertas academica limited.

The role of apoptotic cell clearance in a high-lipid environment:links to ageing

Individuals within the aged population show an increased susceptibility to infection, implying a decline in immune function, a phenomenon known as immunosenescence. Paradoxically, an increase in autoimmune disease, such as rheumatoid arthritis, is also associated with ageing, therefore some aspects of the immune system appear to be inappropriately active in the elderly. The above evidence suggests inappropriate control of the immune system as we age. Macrophages, and their precursors monocytes, play a key role in control of the immune system. They play an important role in host defence in the form of phagocytosis, and also link the innate and adaptive immune system via antigen presentation. Macrophages also have a reparative role, as professional phagocytes of dead and dying cells. Clearance of apoptotic cells by macrophages has also been shown to directly influence immune responses in an anti-inflammatory manner. Inappropriate control of macrophage function with regards to dead cell clearance may contribute to pathology as we age. The aims of this study were to assess the impact of lipid treatment, as a model of the aged environment, on the ability of macrophages to interact with, and respond to, apoptotic cells. Using a series of in vitro cell models, responses of macrophages (normal and lipid-loaded) to apoptotic macrophages (normal and lipid-loaded) were investigated. Monocyte recruitment to apoptotic cells, a key process in resolving inflammation, was assessed in addition to cytokine responses. Data here shows, for the first time, that apoptotic macrophages (normal and lipid-loaded) induce inflammation in human monocyte-derived macrophages, a response that could drive inflammation in age-associated pathology e.g. atherosclerosis. Monoclonal antibody inhibition studies suggest the classical chemokine CX3CL1 may be involved in monocyte recruitment to apoptotic macrophages, but not apoptotic foam cells, therefore differential clearance strategies may be employed following lipid-loading. CD14, an important apoptotic cell tethering receptor, was not found to have a prominent role in this process, whilst the role for ICAM-3 remains unclear. Additionally, a small pilot study using macrophages from young (<25) and mid-life (>40) donors was undertaken. Preliminary data was gathered to assess the ability of primary human monocyte-derived macrophages, from young and mid-life donors, to interact with, and respond to, apoptotic cells. MØ from mid-life individuals showed no significant differences in their ability to respond to immune modulation by apoptotic cells compared to MØ from young donors. Larger cohorts would be required to investigate whether immune modulation of MØ by apoptotic cells contribute to inflammatory pathology throughout ageing.