Search PubMed⌕ Search

Biomedical subjects

Marc A Williams

Publications and source records attributed to Marc A Williams.

6 recordsLinked to original sources
PubMed2003

In vitro cytotoxic effects of stabilizing sugars within human intravenous immunoglobulin preparations against the human macrophage THP-1 cell-line.

Intravenous immunoglobulin (IVIg) is a safe and effective therapy for the treatment of primary and secondary humoral immune deficiencies and autoimmune disorders. Both minor and more serious side effects may occur following IVIg administration in approximately 1-15% of infusions and stabilizing sugars found in IVIg preparations may contribute some of these. In this report, we aimed to determine the cytotoxic effects of IVIg as compared with four stabilizing sugars (glucose, sucrose, maltose and D-sorbitol) found in IVIg preparations on human monocyte-macrophages. The human THP-1 macrophage cell-line was used as a model to determine the effects of stabilizing sugars and IVIg preparations on cell viability and growth. The sugars differentially affected the viability of THP-1 cells. In experiments using doses of the sugars commonly found in IVIg preparations, cell viability and proliferation was unaffected when compared with doses of IVIg typically administered to patients (5 mg/ml). However, in an LDH-release cell lysis assay that measures changes in cell permeability, glucose (50 mg/ml) induced significant release of LDH as compared with complete IVIg (5 mg/ml, p<0.0001). Intranucleosomal DNA fragmentation was not detected at therapeutically relevant doses of IVIg. This suggested that THP-1 cell death was not due to apoptosis. We conclude that osmotic stress mediated by the sugars at high doses promoted THP-1 cell death. We propose that IVIg per se is not cytotoxic to the autonomously growing human THP-1 cell-line but rather, the stabilizing sugars used in the preparations are the cytotoxic factors. This observation was evident when preparations of IVIg were used at high concentrations but not at levels one would associate with clinically relevant doses of IVIg.

Carbohydrates↗
PubMed2002

HIV-1 gp120 modulates the immunological function and expression of accessory and co-stimulatory molecules of monocyte-derived dendritic cells.

Initiation of a primary immune response requires antigen specific CD4(+) T helper (T(h)) cells to assist in priming of CD8(+) cytotoxic T cell (CTL) activity. This is optimal when T(h) cells and CTL recognize antigen when presented to them by a dendritic cell (DC) in the context of major histocompatibility complex (MHC) class I and class II complexes. We have hypothesized that human DC exposed to HIV-1 gp120 IIIB envelope glycoprotein may activate or alter the immunological activation of DCs. Our findings have led us to conclude that HIV-1 gp120 LAV/IIIB activates monocyte-derived DC when they are in their immature state while HIV-1 gp120 exhibits highly selective effects on mature DC. We have observed that following maturation of DCs with lipopolysaccharide (LPS) that they are less susceptible to the modulatory effects of gp120. Although HIV-1 gp120 activates immature DC, it does so in a manner that abrogates their normal function in host immune responses and consequently disturbs the homeostatic balance of host immune response to infection. We suggest that HIV-1 gp120 may support sustained productive infection and transinfection of activated T cells that cluster with gp120-activated DC. We believe that these are promoted by mechanisms that are dependent, at least in part, on altered cytokine responses, enhanced expression of cellular adhesion molecules and augmented DC-mediated activation of T cells in nonspecific and antigen-specific immune reactivities. Consequently, HIV-1 gp120 may actively contribute to the immunopathogenesis of AIDS.

Acquired Immunodeficiency Syndrome↗