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Biomedical subjects

A Sanders

Publications and source records attributed to A Sanders.

At least 19 recordsLinked to original sources

The role of macrophages in the induction and regulation of immunity elicited by exogenous antigens.

Different delivery vehicles may target to different antigen presenting cells (APC) because of their composition, size and/or physical properties. In this study, we examined the priming of cytotoxic T lymphocyte (CTL) responses to a soluble exogenous protein in vivo, using various delivery vehicles. In addition, we determined the role of macrophages as APC in vivo for each of these delivery vehicles by comparing the induction of antigen-specific CTL and serum antibodies in normal and macrophage-depleted mice. Influenza A virus-derived virosomes, liposomes and monophosphoryl lipid A/squalene (MPLSQ) efficiently induced antigen-specific CTL as well as antibody responses, of which virosomes proved to be the most efficient inducers. In mice that were immunized with cell-associated antigen, strong CTL responses but no antigen-specific antibodies were detectable, while aluminium hydroxide and aluminium phosphate elicited antigen-specific antibodies but no CTL responses. Elimination of macrophages in vivo before immunization abrogated CTL responses induced with liposomes and MPL/SQ, but did not affect induction of antigen-specific CTL with virosomes or cell-associated antigen. Importantly, serum antibody levels were not altered after macrophage depletion, regardless of the delivery vehicle used, suggesting that in the absence of macrophages, other APC may phagocytose the exogenous antigens for major histocompatibility complex (MHC) class II processing and presentation. These results suggest that soluble exogenous antigens delivered in different carrier systems may be processed differently by different APC in vivo for MHC class I- or class II-restricted presentation.

Adjuvants, Immunologic

Gender and history of suicidality: are these factors related to U.S. college students' current suicidal thoughts, feelings, and actions?

Gender and history of suicidality (HS vs. NoHS) were related to current symptoms of depression, reasons for living, and reports of self-destructive and life-threatening behavior in a college student sample. Overall, college men reported engaging in more life-threatening and potentially suicidal behavior than college women on the Life Attitudes Schedule (LAS). No gender effects were obtained on the symptoms of depression and reasons for living measures. Results suggest that the LAS may be a particularly effective way to identify college students at risk for self-destructive and suicidal behavior. As expected, HS individuals were more depressed, had fewer reasons for living, and reported engaging in more current suicidal and life-threatening behavior than NoHS participants. However, gender and history of suicidality were found to interact. NoHS women reported avoiding a variety of injury-producing and health-diminishing behaviors that were common for all other groups of college students. Meanwhile, HS women endorsed fewer current reasons for living than did NoHS women, NoHS men, and NoHS men. These findings were interpreted both with regard to cultural and gender-specific expectations for the expression of self-destructive, suicidal, and life-threatening behavior. Implications for the prevention of college women's and men's suicidal behavior were also noted.

Adult

Elimination, blocking, and activation of macrophages: three of a kind?

In mammals, macrophages are multifunctional cells. Apart from their scavenger role in the clearance of non-self materials such as microorganisms and altered-self materials such as apoptotic cells, senescent erythrocytes, immune complexes, and inflammatory products, they play a crucial role in the regulation of both innate and acquired immunity. Whereas the former activity is based on phagocytosis and intracellular degradation, the latter activity largely depends on the production and secretion of a panel of regulatory molecules such as cytokines, chemokines, and nitrogen oxide (NO). Depletion of macrophages and blocking of phagocytosis form important approaches to study the role of these cells in various host defense mechanisms. Moreover, the efficacy of drug- and gene-targeting, based on the application of particulate carrier devices, can be improved in this way. However, compounds originally described as efficacious blockers of phagocytosis simultaneously activate their production of cytokines and NO. Moreover, elimination, blocking, as well as activation of macrophages are all dependent on the concentration of such compounds. When administered in vivo, they will reach some macrophages in a high and others in a low concentration. As a consequence, the former cells may be eliminated or blocked, whereas the latter are activated by the same treatment. In this review, the various methods for suppression of macrophage functions are compared and requirements for the development of new, selective, and organ-specific macrophage-suppressing devices are discussed.

Animals

Transient suppression of macrophage functions by liposome-encapsulated drugs.

Macrophages play an important role in host defense reactions, for example, by phagocytosis of particulate materials. This process also results in the rapid removal of targeting devices such as liposomes and adenovirus vectors and of non-autologous grafted cells and materials. Another aspect of macrophage function is their production and secretion of proinflammatory cytokines. Transient and organ-specific suppression of macrophage function by liposome-mediated manipulation has been shown to improve the efficacy of drug and gene targeting and to reduce the symptoms of inflammatory reactions.

Animals