Movement of methylphenazyl free radicals in polar and nonpolar liquids.

A protonated, charged free radical of methylphenazine methosulfate (PMS) was generated at carbon electrodes in a buffered aqueous medium. This radical diffused from the aqueous phase into nonpolar organic solvents, where it was stable for extended periods. The electron spin resonance (ESR) spectrum of the free radical species in the nonpolar solvent was significantly different from that of the aqueous species. This difference was attributed to the loss of electric charge through deprotonation at the solution interface, followed by solvation of the uncharged species in the organic phase. ESR spectra are presented for PMS free radicals in polar and nonpolar liquid phases, along with electrochemical results and conclusions regarding the mechanisms of movement and toxicity of phenazyl free radicals in biological systems.

Immune complex activation of neutrophils and enhancement of the activation by rheumatoid factor and complement.

The activation of human neutrophils by heat aggregated human immunoglobulin and preformed immune complexes was studied using a chemiluminescent technique. Insoluble aggregates of large size and complexes with antigen/antibody ratios at equivalence produced maximal activation. All responses were enhanced by preincubation with fresh serum. Preincubation of neutrophils with zymosan activated serum also enhanced neutrophil responses. Rheumatoid factor modulated the interaction and in excess reduced all responses, while at optimum concentration caused enhancement. These activation processes result in the release of reactive oxygen metabolites which are considered important inflammatory mediators in the pathogenesis of rheumatoid arthritis.

The mononuclear phagocyte system in experimental chronic marrow failure.

An animal model of chronic hypoplastic marrow failure (CHMF, aplastic anaemia), produced in mice by busulphan, was studied for changes in function and number of tissue macrophage populations. In vitro study of peritoneal macrophages showed no abnormality of function as assessed by chemotaxis, spreading, phagocytosis or bacterial killing. In vivo study of Kupffer cells showed a normal total number and a normal rate of clearance of intravenously injected colloidal carbon. Kupffer cells showed a reduced turnover rate as assessed by a cytoplasmic double-labelling technique and a reduced rate of carbon clearance following stimulation with endotoxin. The numbers of splenic and peritoneal macrophages were both to be decreased and the peritoneal macrophages also showed a decreased recruitment in response to intraperitoneal injection of casein. This decreased recruitment was corrected following marrow transplantation. These observations suggest that in experimental CHMF different tissue macrophage populations are variably decreased in number and that the recruitment of new macrophages is decreased, particularly in response to stimulation. The observations on peritoneal macrophages suggest that at least some of the changes can be directly related to the lesion of marrow precursors.