R Polidori

Serum factors inhibiting some leukocytic functions in Hodgkin's disease

Abstract The presence of leukocyte inhibitory factor(s) (S-LIF) in the serum of patients with Hodgkins disease (HD) has been investigated. It was possible to demonstrate the inhibitory activity in 50% of the patients by employing the agarose plate method. The PHA response in these patients has been found to be reduced. A linear correlation exists between this reduction and the presence of S-LIF in the sera. In order to assess some biological properties of these sera, chemotaxis and phagocytosis of normal cells in the presence of sera from patients with HD have been investigated and both these leukocyte functions have been found to be reduced. The inhibitory capacity was detectable in the same sera which exhibited S-LIF activity and a close linear correlation could be shown. In order to assess whether S-LIF had the same properties of in vitro produced LIF, two monosaccharides were added: l -fucose, capable of blocking the inhibitory activity of LIF, and glucose, which does not block this activity. Surprisingly the addition of l -fucose and glucose greatly enhanced the inhibitory activity of S-LIF. These observations clarify the relationship between the presence of S-LIF and the immunological status in patients with HD and give some indications of the characterization of this (these) factor(s).

In vitro restoration by lithium of defective chemotaxis in Shwachman-Diamond syndrome.

Shwachman-Diamond syndrome is a rare disease characterized by exocrine pancreatic insufficiency, intermittent neutropenia and methaphiseal chondrodysplasia (Shwachman et al, 1964). An increased susceptibility to infections has been observed, although the nature and frequency of infections did not correlate with the degree of neutropenia, so it is reasonable to suppose that, besides neutropenia, other PMN defects may play an important role. Aggett et a1 (1980) showed a constant defect of PMN locomotion: this was in agreement with a multi-system defect of cellular cytoskeleton, since cellular secretion, PMN chemotaxis, and chondrocyte function depend on normal functioning of the microtubular system. More recently, a PMN cytoskeletal defect was shown by the demonstration of an abnormal, patched distribution of Con-A on cell surface (Rothbaun et al. 1982). Recently we demonstrated that lithium can modulate PMN phagocytosis and chemotaxis by modulating the microtubular system. These functions can be improved when impaired, and inhibited when normal, by an increased microtubular assembly, probably mediated by an increase of cGMP (Azzara et al, 1987). Our study concerns an 11-month-old male with exocrine pancreatic insufficiency, normal sweat chloride concentration, metaphyseal dysostosis, growth retardation, normal platelet count, mild anaemia, intermittent neutropenia. and frequent respiratory infections. At the time of the study the absolute PMN count was 0.6 x 109/1 and no evidence of infection was present. PMN phagocytosis was evaluated according to Yamamura et a1 (1977). Briefly, phagocytosis was evaluated as percentage of 3H-Urd uptake inhibition by Saccaromices cerevisiae yeasts in the presence of standard AB serum. Random and stimulated migration were studied by chemotactic chambers, using a modified version (Cates et al, 1978) of the Boyden method. E. coli endotoxin was used as attractant. The cells, separated by dextran and Ficoll density gradient and washed twice, were resuspended in medium or in medium plus lithium carbonate at a concentration of 1.0 mEq/l. No defect was found in phagocytic function (phagocytosis value: 72%: n.v.: 3545%). As regards chemotaxis, random migration showed values of 76.7f 6.4 pm. In the presence of lithium it was slightly enhanced (83.3 f 7.4 pm). Both values are in the normal range (70.6f 13.9 pm. n = 4 9 ) . Stimulated migration was found to be reduced (87 .7 f7 .8 pm) compared with normal (116.4f8.1 pm, n=99). In the presence of lithium PMN migrated 103.3 f 5.1 pm (value in the normal range). The study was performed in triplicate. Our data show a normal behaviour of PMN phagocytosis and random migration, in agreement with previous reports (Ruutu et al, 1984). Stimulated migration was reduced. This function returned to normal with the in vitro use of lithium at a concentration (1.0 mEq/l) which usually inhibits normal PMN chemotaxis by an excess of microtubule aggregation. On the contrary, no significant increase of random motility-which does not depend strictly on microtubules-was detected. This study may be considered as another experimental model to support the hypothesis of a microtubule impairment in the syndrome. Furthermore attempts to achieve significant clinical improvement-although without influence on PMN number-have been very few (Sziits et al, 1984). Our results suggest the therapeutic use of this cation, which moreover is capable of inducing leucocytosis.

Inhibition of leukocyte function by serum from patients with trichinellosis.

Modification of leukocytic function has been reported in only a few human parasitic diseases. In this study we evaluated the effects of the sera from patients infected with Trichinella on chemotactic and phagocytic responses in leukocytes. Leukocyte chemotaxis was tested by the agarose method and phagocytosis by the technique of Yamamura, modified for Saccharomyces cerevisiae. Sera were acquired from patients during a trichinellosis outbreak that occurred in northern Italy in 1986. The parasite was isolated from 1 patient and isoenzymatically typed as Trichinella sp. 3, a new taxon, previously considered Trichinella nelsoni. The results indicated that sera from Trichinella-infected humans inhibited both chemotaxis and phagocytic responses in leukocytes. These findings suggest the existence of serum factor(s) in trichinellosis patients that modify host leukocytic functions. The source and nature of active serum components and the mechanism by which they modulate leukocyte function remain to be clarified.

3H-NECA BINDING TO POLYMORPHONUCLEAR MEMBRANE : EFFECT OF SERA FROM PATIENTS WITH HODGKIN'S DISEASE

Several studies have shown that sera from patients with Hodgkins disease contain factors capable of inhibiting polymorphonuclear functions, among them chemotaxis. In the present study, we investigated whether these sera, which were able to inhibit PMN chemotaxis in the agarose test, were also able to affect the 3H-NECA binding to PMN membrane obtained from healthy donors. Control experiments were carried out using PMN incubated with a pool of sera from healthy volunteers. No significant difference was found in the maximum number of binding sites; on the contrary, the equilibrium dissociation constant was significantly increased in the membrane preparation of PMN incubated with pathological serum.