Biomedical subjects

Charles F Anderson

Publications and source records attributed to Charles F Anderson.

5 recordsLinked to original sources

PubMed2002

Generalized derivation of an exact relationship linking different coefficients that characterize thermodynamic effects of preferential interactions.

In solutions consisting of solvent water (component '1') and two solute components ('2' and '3'), various thermodynamic effects of differences between solute-solute and solute-solvent interactions are quantitatively characterized by state functions commonly called 'preferential interaction coefficients': gamma(mu(1),mu(3)) triple bond (delta(m3)/delta(m2))(T,mu(1),mu(3)) and gamma(mu(k)) triple bond (delta(m3)/delta(m2))(T,P,mu(k)), where k = 1,2 or 3. These different derivatives are not all directly accessible to experimental determination, nor are they entirely equivalent for analyses and interpretations of thermodynamic and molecular effects of preferential interactions. Consequently, various practical and theoretical considerations arise when, for a given system, different kinds of preferential interaction coefficients have significantly different numerical values. Previously we derived the exact relationship linking all three coefficients of the type gamma(mu(k), and hence identified the physical origins of the differences between gamma(mu(1)) and gamma(mu(3)) that have been experimentally determined for each of various common biochemical solutes interacting with a protein [J. Phys. Chem. B, 106 (2002) 418-433]. Continuing our investigation of exact thermodynamic linkages among different types of preferential interaction coefficients, we present here a generalized derivation of the relationship linking gamma(mu(1),mu(3)), gamma(mu(3)) and gamma(mu(1)), with no restrictions on m(2), m(3) or any physical characteristic of either solute component (such as partial molar volume). Hence, we show that (gamma(mu(1),mu(3)) - gamma(mu(3))) is related directly to (gamma(mu(3)) - gamma(mu(1))), for which the physical determinants have been considered in detail previously, and to a factor dependent on the ratio of the partial molar volumes V3/V1. Our generalized expression also provides a basis for calculating gamma(mu(1),mu(3)), even in situations where preferential interactions could not be investigated by equilibrium dialysis. To demonstrate this applicability, we analyze isopiestic distillation data for aqueous solutions containing urea and NaCl, two small solute components that cannot be selectively dialyzed.

Thermodynamics↗

PubMed2002

Cutting edge: biasing immune responses by directing antigen to macrophage Fc gamma receptors.

An immune response can deviate toward either a Th1- or Th2-like response. In this work we examine the contribution that activated macrophages and IgG Abs make toward this deviation. The use of activated macrophages as APCs resulted in a strong polarized T cell response that was predominated by IFN-gamma. However, when Ag was targeted to FcgammaRs on these macrophages, the T cell response was reversed and biased toward a Th2-like response. This Th2-like phenotype was stable and was retained when the T cells were subsequently restimulated under nonbiasing conditions. The T cell biasing and its reversal via FcgammaR was also observed in vivo. Mice vaccinated with IgG-opsonized OVA made high levels of IgG Ab of the IgG1 isotype. These studies demonstrate that the ligation of FcgammaR on activated macrophages can reverse the Th1 biasing that occurs as a result of innate immune responses to microbial products.

Adjuvants, Immunologic↗

PubMed2002

Differential SLP-76 expression and TCR-mediated signaling in effector and memory CD4 T cells.

We present in this study novel findings on TCR-mediated signaling in naive, effector, and memory CD4 T cells that identify critical biochemical markers to distinguish these subsets. We demonstrate that relative to naive CD4 T cells, memory CD4 T cells exhibit a profound decrease in expression of the linker/adapter molecule SLP-76, while effector T cells express normal to elevated levels of SLP-76. The reduced level of SLP-76 is memory CD4 T cells is coincident with reduced phosphorylation overall, yet the residual SLP-76 couples to a subset of TCR-associated linker molecules, leading to downstream mitogen-activated protein (MAP) kinase activation. By contrast, effector CD4 T cells strongly phosphorylate SLP-76, linker for activation of T cells, and additional Grb2-coupled proteins, exhibit increased associations of SLP-76 to phosphorylated linkers, and hyperphosphorylate downstream Erk1/2 MAP kinases. Our results suggest distinct coupling of signaling intermediates to the TCR in naive, effector, and memory CD4 T cells. Whereas effector CD4 T cells amplify existing TCR signaling events accounting for rapid effector responses, memory T cells engage fewer signaling intermediates to efficiently link TCR triggering directly to downstream MAP kinase activation.

Adaptor Proteins, Signal Transducing↗

PubMed2002

Modulating macrophage function with IgG immune complexes.

Macrophages respond to bacterial products by releasing a large array of inflammatory mediators. We demonstrate that, in the presence of IgG immune complexes, macrophages produce high levels of IL-10 and virtually no IL-12, when they are exposed to bacterial products. The production of IL-10 by these cells can dampen innate inflammatory responses to microbial products, such as LPS. This alteration in macrophage cytokine production can also influence an adaptive immune response, preferentially inducing Th2-type immunity. Thus, immune complexes change the physiology of activated macrophages, converting them to anti-inflammatory cells that induce Th2-like immune responses. We have termed these cells type II activated macrophages.

Antigen-Antibody Complex↗

PubMed2002

A novel phenotype for an activated macrophage: the type 2 activated macrophage.

Activated macrophages were used as antigen presenting cells (APCs) to determine the extent to which these APCs could influence an adaptive immune response. We show that activated macrophages induced a strong polarized Th1-like T cell response that was predominated by IFN-gamma. However, when antigen was targeted to Fcgamma receptors on these macrophages, their phenotype changed, and they now induced a T cell response that was predominated by IL-4. The initial biasing by activated macrophages toward a Th1-like response was a result of activation of the innate immune response, as macrophages from MyD88(-/-) mice failed to produce Th1-inducing cytokines. The reversal of the Th1 biasing was a result of FcgammaR ligation, as macrophages lacking the FcR common gamma chain failed to reverse this biasing. To show that this biasing could occur in vivo, mice were injected with activated macrophages or activated macrophages whose FcgammaR had been ligated with an irrelevant immune complex. Mice injected with FcgammaR-ligated macrophages made more antibody than those receiving conventionally activated macrophages, and the antibody was predominantly of the IgG1 isotype. These studies demonstrate that FcgammaR ligation on activated macrophages can change the phenotype of these APCs to cells that preferentially drive a Th2-like response. We have termed these cells type 2 activated macrophages.

Adaptor Proteins, Signal Transducing↗