The antifilarial activity of a novel group of organic arsenicals upon Brugia pahangi.

Mel W is a second generation anionic organic arsenical which is filaricidal but has sporadic and unacceptable lethal side effects. Eight new cationic derivatives have now been synthesized in an attempt to avoid the side effects and have been examined for their effects upon adult Brugia pahangi in Meriones unguiculatus. They were all shown to be potent filaricides and the two best compounds, Mel Ga and Mel Cy, were at least 95% effective in killing adult B. pahangi at 5 X 3.13 mg/kg when injected subcutaneously.

The induction of functional mononuclear and multinuclear macrophages in murine brugian filariasis: morphological and immunological properties.

This present study describes the ontogeny and morphology of mononuclear and multinuclear macrophages in murine Brugia pahangi infections. Intraperitoneal infection with L 3 resulted in the development of adult worms and the production of microfilariae in many mice; however, all worms were usually removed by 100 days post infection (p.i.). The infection induced predominantly mononuclear and multinuclear macrophage responses in the peritoneal cavity, with maximum numbers of peritoneal cells being achieved by 8-12 weeks p.i. and at this time some 20% of the macrophages were multinucleated. Lymphocyte numbers were also increased during infection. The reactions around the filariae involved macrophages (both single and multinucleated), eosinophils, fibroblasts and the laying down of collagen. Most worms were involved in these cellular reactions by 5-6 weeks p.i., with the multinuclear macrophages generally seen lying close to the parasites. All stages of parasites developed vacuolar internal changes early in their degeneration with calcification being a later change. The destruction and removal of the sheath was not apparently a prerequisite for degeneration of the body of microfilariae. Rosetting techniques showed that 75% of peritoneal cells (macrophages) in infected animals possessed Fc receptors compared with 32% of those in uninfected mice, and for C3 receptors the respective results were 35% and 5%. The multinuclear cells possessed both types of receptors at levels similar to those of mononuclear macrophages. Likewise both cell types were found to readily phagocytose yeast and latex particles, as well as staining positively for non-specific esterases.(ABSTRACT TRUNCATED AT 250 WORDS)

Mononuclear and multinuclear macrophages in filarial infections.

Filarial infections commonly involve chronic tissue responses to these complex and resiliant organisms. These responses, which occur with a number of the parasitic stages of filariae, involve macrophages, and these cells appear to be important in immunologically induced destruction and removal of these important parasites of man and animals. Details of their presence and experimental induction as well as their distinction into a number of morphological types, including multinuclear (giant cell) forms, is described in this communication. The ability of these various forms to function in phagocytic and immunologically mediated adherence assays is also described.

Increased activity of macrophages from mice infected with Brugia pahangi: in vitro adherence to microfilariae.

After the inoculation of infective larvae of Brugia pahangi into the peritoneal cavities of CBA/Ca mice adult worms developed, but by 12 weeks post-infection the parasites were usually dead and surrounded by granulomatous tissue. Macrophages were the most common cell type in these granulomas and were also found in increasing numbers free in the peritoneal cavity. We have investigated the ability of macrophages to damage microfilariae in vitro, in a system where microfilariae were cultured together with cells and serum taken from either uninfected female CBA/Ca mice or at various intervals after infection. Macrophages adhered to and killed microfilariae in this system and there was an increase in vitro adherence of these cells during the course of infection. The peak level of in vitro activity of these cells coincided with the phase of parasite killing in vivo. The presence of serum also affected the degree of macrophage adherence and subsequent death of the parasite. Analysis of serum components using EGTA, zymosan or heat inactivation suggested that complement and possibly heat labile antibody were involved. Immunoglobulins were shown by immunofluorescence to be present on the surface of microfilariae cultured in serum from infected mice. It is concluded from this study that macrophages are actively involved in the termination of murine filarisis.