Role of phagocytic cells in cancer

Partial manifestations of the anti-tumor defence in the organism will sometimes lead to surprising changes in the clinical picture of the disease. This must be taken into consideration and, if possible, such therapeutical procedures must be chosen which do not interfere with the course of defence reactions. Therefore, the study of the organism's anti-tumor defence mechanisms is of theoretical as well as of practical value. In Hodgkin's disease a significant increase in phagocytic activity could be observed when the disease was in progress; during clinical remission the values returned to normal ones [181]. The phagocytic activity may be supposed to reflect the dynamic situation between the host and the tumor in man [196]. The determination of phagocytic activity may be useful as an indicator of the extent or activity of the disease [181]. Phagocytic function may be affected by a surgical intervention [46], radiotherapy [179, 183] and by anti-tumor chemotherapy [3, 209]. On stimulating MPS during the course of radiotherapy, improved clinical results have been observed [115]. When examining patients in the course of treatment and after it, a need was felt for methods that can easily be applied and that enable the state of the defence capacity of the organism to be taken into account. The measurement of the phagocytic activity of MPS in clinical practice by using the 131I labelled aggregated human albumin [115] can only be used at selected workplaces. Today, however, drugs and therapeutical procedures with immunosuppressive effects are virtually used in all workplaces where there are patients with malignant tumors. Therefore, an original method of phagocytosis of latex particles in vitro has been elaborated. This method is primarily aimed at orientation, but it may be employed in every hematological laboratory. It determines the intensity of phagocytic activity of leukocytes. The differences between the values obtained in cancer and those obtained in healthy subjects and patients with non-malignant disorders are highly significant. This statement has been made on the basis of 363 examinations performed in clinically healthy subjects, in patients with cancer and in patients with non-malignant disorders. The results were analyzed statistically and it has been found out that the phagocytic capacity of leukocytes is significantly activated in the presence of a pathological process in the organism. This activation is mush more evident in cancer patients than in patients with non-malignant disorders. Strikingly low values were observed in the terminal stage of the disease when the defence capacity of the organism has broken down. These findings induced us to consider the suitability of this kind of examination. It can be used alone or in combination with other methods for estimating the defence capacity of the organism, or for choosing the right therapeutical measures...     

Monitoring of polymorphonuclear leukocyte functions in diabetes mellitus— a comparative study of conventional radiometric function tests and low-light imaging systems

In this study neutrophil (PMN) phagocytic capacity was investigated using a conventional radiometric ingestion assay (IN) in comparison with PMN respiratory burst activity assessed by luminol-enhanced chemiluminescence (LCL) in response to phorbolesters and LCL induction during phagocytosis of opsonized Staphylococous aureus (STLCL) in diabetes mellitus and healthy controls. PMN ingestion was measured with ³H-thymidine-labelled S. aureus in a kinetic radiometric assay. LCL and STLCL were assessed in a parallel detecting microtitre-plate luminometer (MTP-Reader). PMN of diabetic subjects showed a highly significant reduction of peak LCL in response to PMA as well as during phagocytosis of S. aureus (STLCL) compared to non-diabetic controls (p<0.001 respectively). PMN ingestion in diabetic patients (51.8±4.6%) was significantly reduced compared to controls (78.3±6.2%) (p<0.01). The in vitro data displayed impaired PMN oxidative burst activity at glucose concentrations ? 13.8mmol/L, whereas PMN IN was significantly reduced at glucose levels ?27.75mmol/L. The control group showed a positive correlation of peak LCL response and IN (p<0.05) but not of STCL and IN; in diabetic patients this was also true, but did not reach statistical significance. The data obtained in this study clearly demonstrated impaired PMN respiratory burst activity and markedly reduced phagocytic PMN functions in diabetic patients ex vivo and in vitro as measured by LCL and by ingestion of ³H-thymidine-labelled S. aureus suggesting inhibitory effects of elevated glucose concentrations on various PMN-functions, which might be of clinical importance concerning altered host defence.     

A novel post-translational incorporation of tyrosine into multiple proteins in activated human neutrophils. Correlation with phagocytosis and activation of the NADPH oxidase-mediated respiratory burst.

Activation of human neutrophils by PMA causes a post-translational incorporation of 14C-labeled tyrosine into multiple neutrophil (PMN) proteins, that is distinctly different from the enzymatic tyrosinolation of tubulin in FMLP-stimulated PMN. Post-translational incorporation of other radiolabeled amino acids, including the structurally similar amino acid phenylalanine, does not occur under identical conditions of neutrophil activation, suggesting an involvement of the phenolic hydroxyl group of tyrosine in the PMA-mediated reaction. Similar to the stimulation of PMN tubulin tyrosinolation by FMLP, the PMA-induced incorporation of tyrosine into multiple PMN proteins is closely associated with activation of the NADPH oxidase-mediated respiratory burst in stimulated PMN and can be inhibited by a variety of reducing agents, inhibitors of peroxidase-mediated reactions, and intracellular scavengers of oxygen radicals. Moreover, the PMA-induced post-translational incorporation of tyrosine does not occur in PMN from patients with chronic granulomatous disease and is significantly reduced (50%) in PMN of an individual with myeloperoxidase deficiency. A similar stimulus-induced incorporation of tyrosine into multiple PMN proteins is also observed in PMN exposed to various phagocytic stimuli, and the incorporated radioactivity in cells undergoing phagocytosis is substantially enriched (40- to 50-fold) in isolated PMN phagolysosomes. Consistent with this latter observation, HPLC fractionation of stimulated PMN proteins and analysis of the incorporated radioactivity reveal that the 14C label is primarily associated with PMN membrane proteins. Furthermore, this post-translational incorporation of tyrosine, like that associated with PMA stimulation, is associated with production of oxygen radicals and the generation of protein carbonyl derivatives, which are indicative of oxidative protein modifications via mixed function oxidases. Our findings indicate that tyrosine incorporation into membrane proteins of stimulated PMN is functionally relevant to the physiologic host-defense responses of human neutrophils undergoing phagocytosis.     

Localization of NADH oxidase on the surface of human polymorphonuclear leukocytes by a new cytochemical method

The ultrastructural localization of NADH oxidase, a possible enzyme in the increased oxidative activity of polymorphonuclear leukocytes (PMN) during phagocytosis, was studied. A new cytochemical technique for the localization of H2O2, a product of NADH oxidase activity, was developed. Cerous ions, in the presence of peroxide, form an electron-dense precipitate. Resting and phagocytically stimulated PMN were exposed to cerous ions at pH 7.5 to demonstrate sites of NADH-dependent, cyanide-insensitive H2O2 production. Resting PMN exhibites slight activity on the plasma membrane; phagocytizing PMN had extensive deposits of reaction product localized within the phagosome and on the plasma membrane. Peroxide involvement was demonstrated by the inhibitory effect of catalase on cerium precipitation; the surface localization of the enzyme responsible was confirmed by using nonpenetrating inhibitors of enzymatic activity. A correlative study was performed with an NADH-dependent, tetrazolium-reduction system. As with cerium, formazan deposition on the surface of the cell was NADH dependent, cyanide insensitive, and stimulated by phagocytosis. Superoxide dismutase did not inhibit tetrazolium reduction, as observed cytochemically, indicating direct enzymatic dye reduction without superoxide interposition. These findings, combined with oxygen consumption studies on resting and stimulated PMN in the presence or absence of NADH, indicate that NADH oxidase is a surface enzyme in human PMN. It is internalized during phagocytosis and retains its peroxide-generating capacity within the phagocytic vacuole.     

Effect of phagocytosis by human polymorphonuclear leukocytes and rabbit alveolar macrophages on 2-deoxyglucose transport.

2-Deoxyglucose transport was characterized in human polymorphonuclear leukocytes (PMN) and rabbit alveolar macrophages (AM). The Km was 1 mM for human PMN and 1.6 mM for rabbit AM, and the Vmax was 0.66 x 10(-3) micromoles/45 sec/10(6) PMN and 5.09 x 10(-4) micromoles/45 sec/10(6) AM. The rate of 2-deoxyglucose transport was the same before and after phagocytosis in PMN from normal individuals and three patients with chronic granulomatous disease, as well as rabbit AM. Studies of the kinetics of 2-deoxyglucose transport and intracellular fate of 2-deoxyglucose in human PMN indicate that the nature of the membrane transport system is not altered by phagocytosis. The results support the concept that the plasma membrane is mosaic in character with geographically separate transport and phagocytic sites.     

Metabolic activity of phagocytes in experimental sporotrichosis

Phagocytosis plays an important role as a protective mechanism against infections, since polymorphonuclear leukocytes (PMN) and macrophages are the first cellular lines opposed to agressive microorganisms. In patients with sporotrichosis a diminished capability of killing engulfed yeast by their PMN has been described, but the origin of this deficiency remains unknown.In this work, partial aspects of the oxidative metabolism of PMN leukocytes and peritoneal macrophages of mongolian gerbils experimentally infected with sporotrichosis were studied. For this purpose the nitroblue tetrazolium (NBT) test as described by Baehner and Nathan (1) and myeloperoxidase activity measured according to Kaplow's method were utilized.The PMN and macrophages of mongolian gerbils infected with sporotrichosis showed increased reduction of NBT when compared with the phagocytic cells of normal ones, as is usually observed in most infections. Myeloperoxidase activity was diminished in both PMN and macrophages, but this diminution was statistically significant only in PMN leukocytes. These results show that part of the oxidative mechanisms of phagocytic cells can be impaired in experimental sporotrichosis, and could be correlated with the diminished fungicidal activity of PMN leukocytes obtained from patients infected with sporotrichosis.     

Monokines released during short-term Fc gamma receptor phagocytosis up-regulate polymorphonuclear leukocytes and monocyte-phagocytic function.

Freshly explanted monocytes phagocytosing IgG antibody-coated erythrocyte targets (EIgG) release a factor(s) that stimulates phagocytosis by neighboring monocytes and polymorphonuclear leukocytes (PMN). Culture supernatants obtained after 30-min incubation of adherent monocytes with EIgG, but not unopsonized sheep erythrocytes, markedly up-regulated the extent of PMN phagocytosis and enhanced the rate at which monocytes ingested EIgG. The presence of this factor(s) was first evident in phagocytic studies in which monocytes were prepared by a colloidal silica-based continuous gradient technique (Sepracell-Mn). After introduction of erythrocyte targets, there was a 20- to 30-min delay before initiation of phagocytosis that was not observed with monocytes prepared by the standard Percoll-gradient technique. Experiments suggest that, when compared with monocytes prepared by the Percoll-gradient method, Sepracell-Mn monocytes are closer to a base line state of activation with regard to the expression of Fc gamma RI and the ability to ingest EIgG. The mechanism of PMN upregulation by the monocyte factor(s) was explored. Monocyte supernatants did not induce an increase in the surface expression of PMN Fc gamma RI, II, or III. Neither anti-TNF, anti-IL-2, nor anti-GM-CSF had any significant effect on monocyte supernatant activity. Neutrophil activating protein-1 was not detected by ELISA. In contrast, anti-IL-1 completely blocked the effect of the supernatant on subsequent monocyte phagocytosis, and partially inhibited its effect on PMN phagocytosis. Furthermore, it was shown that RIL-1 as well as TNF markedly enhanced monocyte and PMN ingestion of EIgG. These results suggest that monocytes, after Fc gamma R-mediated phagocytosis, release monokines, including at least IL-1, which enhance the phagocytic function of neighboring PMN and monocytes to augment the host defense process.     

Indices of phagocytosis of S and R forms of Brucella in patients with acute and chronic brucellosis caused by Brucella abortus

The characteristics of phagocytosis (phagocytic activity and phagocytic index) in patients with acute and chronic brucellosis have been studied with B. abortus S- and R-forms used as its objects. The study has revealed that higher characteristics of phagocytosis with respect to B. abortus S-forms are observed in patients with acute brucellosis, whereas in patients with chronic brucellosis taking a benign course phagocytosis is more intensive in respect of R-forms. In patients with frequent exacerbations of chronic brucellosis differences in the characteristics of phagocytosis with respect to B. abortus S- and R-forms are not statistically valid.     

Effects of beta-carotene, selenium and vitamin A on in vitro polymorphonuclear leukocytic activity in peripartal buffalo (Bubalus bubalus)

The effect of different concentrations of three antioxidans on phagocytic and kill activities of blood polymorphonuclear leukocytes (PMN) isolated from buffaloes during the peripartum period (4 weeks before to 7 weeks after parturition) was investigated in this study. Two concentrations of beta-carotene and vitamin A (10(-6) and 10(-5) M) and one concentration of Se (10(-9) M) were used. Phagocytic activity of PMN treated with beta-carotene (10(-6)M) significantly enhanced (P < 0.05) after parturition (Week 0 until Week 3), whereas the kill activity of the same cells significantly (P < 0.05) increased before and after parturition (at Weeks -4, -3, -2, 0, 1, 2 and 3). The concentration of beta-carotene (10(-5) M) enhanced phagocytosis of PMN only at Weeks 0 and 1 and kill activity at Weeks -4, -3, -2, 0, and 1. Selenium (10(-9)M) significantly (P < 0.05) enhanced phagocytic activity of PMN starting from parturition (Week 0) until Week 3 postpartum. Kill activity increased significantly both before (Weeks -4, -3 and -2) and after (Weeks 0, 1, 2, 3 and 4) parturition. Vitamin A (10(-6) M) significantly enhanced phagocytic activity of PMN at Weeks 0, 1, and 2, whereas, the concentration of beta-carotene (10(-5) M) increased phagocytic activity only at Week 0. Kill activity of PMN increased significantly (P < 0.05) at Weeks -1 and 0 (10(-6)M). These results demonstrate that beta-carotene and selenium significantly enhanced phagocytic and kill activities of PMN isolated from buffaloes around parturition in vitro. Vitamin A enhanced phagocytosis and kill activities but not to the same extent as beta-carotene and selenium. Apparently, the in vitro killing activity of PMN is a distinctive function from phagocytosis and both activities may be enhanced by the use of essential nutrients, especially during the peripartum period. Moreover, beta-carotene is more effective as an antioxidant than vitamin A in enhancing the activities of phagocytic cells.     

Generation of reactive forms of oxygen by polymorphonuclear leukocytes during hepatoma growth in the peritoneal cavity of animals]

In the present work, an attempt was made to analyse generation of reactive oxygen species (ROS) by polymorphonuclear leucocytes (PMN) in the course of tumour growth, using chemiluminescence (CL). A multiple increase in the capacity of polymorphonuclear leucocytes of generating active forms of oxygen in the course of tumor growth was discovered. Two causes of this process were found. 1) the increase in specific activity of leucocytes; 2) the increase in the total quantity of PMN circulating in the blood. Leucocytes were also found in the ascite liquid. PMN leucocytes were shown to participate in the antitumor defence of the organism.     

Defective neutrophil function in the autoimmune mouse strain MRL/lpr. Potential role of transforming growth factor-beta.

Patients with systemic autoimmune diseases such as SLE and rheumatoid arthritis have increased rates of morbidity and mortality caused by infection. Although this increased risk of infection has been primarily attributed to therapeutic immuno-suppression, some reports exist of defective polymorphonuclear leukocytes (PMN) function in these patients. The purpose of the present work is to investigate the recruitment of PMN phagocytic function in a murine model of autoimmunity, the MRL/lpr mouse. PMN from MRL/lpr, but not from congenic MRL/n mice, exhibit a marked defect in the amplification of FcR-mediated phagocytosis stimulated by various inflammatory mediators. This defect is acquired and correlates with the onset of the autoimmune disease observed in this strain. In addition, MRL/lpr but not MRL/n PMN exhibit a defect in extravasation into the thioglycollate-inflamed peritoneum. Incubation of MRL/n PMN in MRL/lpr serum induces a defect in the amplification of PMN phagocytic function identical to that observed with MRL/lpr PMN. The activity in the serum that induces this defect is neutralized by an antibody to TGF-beta but not by control antibodies. Incubation of murine and human PMN with purified TGF-beta induces an identical defect in stimulated FcR-mediated ingestion. In addition, TGF-beta-treated MRL/n PMN fail to extravasate into the thioglycollate-inflamed peritoneum after injection into normal MRL/n recipient mice. In addition, direct injection of TGF-beta into MRL/n mice also reduces the percentage and number of PMN in the thioglycollate-stimulated peritoneal exudates of these mice. The defect in PMN extravasation and phagocytic function was not caused by failure of the defective PMN to modulate the expression of the adhesion molecules, Mac-1 and Mel-14. These data indicate that defects in PMN function can be observed in a murine model of autoimmunity and that spontaneous production of TGF-beta possibly may play a crucial role in the pathogenesis of the defective PMN function in this animal model.     

Influence of HIV-infection on the phagocytic activity of monocytes/macrophages and granulocytes

Because of the great importance of phagocytosis as a key process in host defence, the influence of HIV-infection on the phagocytic activity of monocytes/macrophages (M0/MAC) and granulocytes was investigated. Therefore, blood samples from the peripheral blood of 70 HIV-infected individuals were incubated with fluorescein isothiocyanate (FITC) labeled Escherichia coli. The uptake of the bacteria was monitored by flow cytometer analysis. A strong and significant increase in the relative number of phagocytic granulocytes was observed ranging from 12.8% in an uninfected control collective to over 30% in AIDS patients. This effect was obtained for all patients and independent of the stage of disease. For monocytes, only marginal changes were found in their phagocytic function. These data suggest that the high susceptibility of HIV patients for secondary infections is not linked to a loss of phagocytic ability of monocytes/macrophages and/or granulocytes.     

Lyme borreliosis in central Italy (1995-1998)

From January 1995 to July 1998, 340 serum samples collected in Central Italy from patients clinically suspected of having Lyme borreliosis were investigated. All samples were tested for the presence of antibodies to B. burgdorferi by Elisa. The Elisa positive samples were subjected to further tests by Western Blot for confirmation. Out of 340 patients, 13 (3.8%) proved to be B. burgdorferi positive, while 9 (2.6%) were found to have Lyme disease with seroprevalence being higher in these latter than that of blood donors from Central Italy. Our results indicate that Lyme borreliosis is present in Central Italy. A comparison between Italian and European studies reveals that Lyme disease is still underestimated in Italy, the main reason being that a monitoring system for the study of Lyme borreliosis was only established in 1990.     

Effects of Porphyromonas gingivalis culture products on human polymorphonuclear leukocyte function

Abstract Porphyromonas gingivalis culture supernate was found to induce hemotypic agglutination of human polymorphonuclear leukocytes (PMN). Pretreatment of PMN with P. gingivalis supernate inhibited both the rate and the degree of aglutination induced by the secretagogues PMA and FMLP. Lipopolysaccaharide from P. gingivalis upregulated the CR3 (Mac-1, CD11b) receptors of PMN. Treatment of glass-adherent PMN with P. gingivalis supernate did not alter their phagocytic capacity fot P. gingivalis cells but when PMN were treated in suspension the cells adhered less well to glass and phagocytosis of those PMN that did adhere was reduced. P. gingivalis supernate treatment of PMN induced lysozyme release but the amount released during phagocytosis when supernate was present did not change. Neither P. gingivalis supernate nor LPS were cytotoxic for PMN. The data suggest that P. gingivalis factors could interfere with PMN elimination of this organism at the site of infection by inappropriately stimulating PMN, depressing phagocytosis and causing enhanced CR3 expression. The consequent agglutinatin or enhanced adherence could also lead to decreased phagocytic capacity of the adherant or agglutinated cells.     

Effect of rhIL-15 on TLR2 expression and apoptosis of PMN from patients with Lyme disease

In this study we estimated the expression of TLR2 and apoptosis of PMN in patients with Lyme disease. The cells were isolated from heparinized whole blood by Gradisol G gradient and incubated 18 h with rhIL-15 and LPS. Expression of TLR2 was estimated in lysates of PMN by western blot, apoptosis of PMN by immunofluorescent analysis. The results obtained revealed the higher expression of TLR2 in PMN and higher percentage of apoptosis PMN in patients with Lyme disease compared with control. We observed an effect of rhIL-15 on the increased expression of TLR2 in PMN and the increased survival of PMN isolated from patients with Lyme disease. These findings suggest that IL-15 has the ability to modulate of neutrophil response against Borrelia burgdorferi.     

Phagocytosis of immunoglobulin G and C3-bound human sperm by human polymorphonuclear leukocytes is not associated with the release of oxidative radicals.

Antisperm antibody (ASA)- and complement (C)-mediated immune injury to human sperm is thought to be caused in part by phagocytic neutrophils. To investigate this process, we co-cultured purified human polymorphonuclear leukocytes (PMN) with swim-up sperm in the presence of ASA-positive and ASA-negative sera and assayed for PMN respiratory burst activity, monitored by the release of superoxide anion (O2-) and hydrogen peroxide (H2O2). Phorbol myristate acetate (PMA) and opsonized zymosan were used as positive controls. Phagocytosis of ASA-positive and C-bound sperm by PMN did not enhance O2- production when compared to incubation of sperm with ASA-negative sera. Phagocytosis of ASA-positive and C-bound sperm also resulted in minimal release of H2O2 when compared with ASA-positive and C-negative sperm that were not phagocytosed. In contrast, PMN were maximally stimulated to release O2- in response to either opsonized zymosan or PMA. The kinetics of PMA-induced O2- release was unaffected by the presence of ASA-positive and C-bound sperm. Cytocentrifuge preparations of PMN incubated with ASA-positive and C-bound sperm revealed limited O2- release at the site of PMN/sperm contact. These results indicated that 1) phagocytosis of motile sperm by PMN requires the binding of both ASA and C to the sperm surface; 2) phagocytosis of ASA-positive and C-positive sperm by PMN fails to release reactive oxygen species; and 3) metabolic processes associated with PMN respiratory burst activity may not be coupled to the ingestion of ASA-positive and C-bound sperm.     

Reactive oxygen intermediates enhance Fc gamma receptor signaling and amplify phagocytic capacity.

Receptors for the Fc region of IgG (Fc gamma R) mediate internalization of opsonized particles by human neutrophils (PMN) and mononuclear phagocytes. Cross-linking of Fc gamma R leads to activation of protein tyrosine kinases and phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) within Fc gamma R subunits, both obligatory early signals for phagocytosis. Human PMN constitutively express two structurally distinct Fc gamma R, Fc gamma RIIa and Fc gamma RIIIb, and can be induced to express Fc gamma RI by IFN-gamma. We have previously shown that stimulation of PMN through Fc gamma RIIIb results in enhanced Fc gamma RIIa-mediated phagocytic activity that is inhibited by catalase. In the present study, we have tested the hypothesis that reactive oxygen intermediates (ROI) have the capacity to regulate Fc gamma R responses and defined a mechanism for this effect. We show that H2O2 augmented phagocytosis mediated by Fc gamma RIIa and Fc gamma RI in PMN and amplified receptor-triggered tyrosine phosphorylation of Fc gamma R-associated ITAMs and signaling elements. Generation of endogenous oxidants in PMN by cross-linking Fc gamma RIIIb similarly enhanced phosphorylation of Fc gamma RIIa and Syk, a tyrosine kinase required for phagocytic function, in a catalase-sensitive manner. Our results provide a mechanism for priming phagocytes for enhanced responses to receptor-driven effects. ROI generated in an inflammatory milieu may stimulate quiescent cells to rapidly increase the magnitude of their effector function. Indeed, human monocytes incubated in the presence of stimulated PMN showed oxidant-induced increases in Fc gamma RIIa-mediated phagocytosis. Definition of the role of oxidants as amplifiers of Fc gamma R signaling identifies a target for therapeutic intervention in immune complex-mediated tissue injury.     

TLR2 expression in relation to IL-6 and IL-1beta and their natural regulators production by PMN and PBMC in patients with Lyme disease

Recently, it has been reported that TLR2 on macrophages plays a unique role in the inflammatory response and host defense to infection with Borrelia burgdorferi (Bb) which is an etiologic agent of Lyme disease. Experimental studies show that PMNs also play an essential role in infection control by Bb. However, there is no available data about TLR2 expression on PMN in the course of Lyme disease. In the present study, TLR2 expression and production of IL-1beta and IL-6 as well as their natural regulators (sIL-1RII, IL-1Ra and sIL-6Ralpha, sgp130, resp) by PMN of peripheral blood in patients with Lyme disease were examined. For the purpose of comparison, the same activity of autologous peripheral blood mononuclear cells (PBMCs) was estimated. An effect of rhIL-15 on TLR2 and cytokine secretion was also studied. Increased TLR2 expression in unstimulated neutrophils suggests an important role of these cells in mechanism recognition of B burgdorferi in patients with Lyme disease. The relationship between IL-1beta and IL-6 as well as their regulators by unstimulated PMN and PBMC, observed in the present study, may lead to enhanced IL-6- and to inhibition of IL-1beta-mediated reactions in this patient group. Changes in the TLR2 expression after rhIL-15 stimulation appear to have a favorable effect on mechanism recognition of Bb. The relations between IL-6 and its regulators (sIL-6Ralpha and sgp130) as well as between IL-1beta and its regulators (IL-1Ra and sIL-1RII) after rhIL-15 stimulation may lead to enhanced IL-1beta- and IL-6-mediated inflammatory reactions in the course of Lyme disease.     

Differences in the respiratory burst of human polymorphonuclear leukocytes induced by virulent and avirulent Legionella pneumophila Serogroup 1

Two strains of Legionella pneumophila of different virulence were examined for their influence on the metabolic oxidative activity of human polymorphonuclear leukocytes. The leukocytes exhibited decreased rates of oxygen consumption and diminished chemiluminescence activity following phagocytosis of a virulent strain of L. pneumophila serogroup 1. In contrast, phagocytosis of its multipassaged derivative rendered avirulent, was accompanied by increased rates of both oxygen consumption and chemiluminescence activity. Although no differences were observed in oxygen uptake induced by the virulent legionellae compared to leukocytes at rest, statistically significant differences were observed in the chemiluminescence responses. These observations were not unexpected, since the luminol-enhanced chemiluminescence assay, is more sensitive than the oxygen uptake assay. In spite of decreased metabolic activity of PMN in the presence of virulent legionellae, electron microscope studies showed higher numbers of intracellular L. pneumophila than the avirulent subtype. Thus, virulent and avirulent L. pneumophila can be differentiated on the basis of oxygen consumption and chemiluminescence assays.     

The effect of leukinferon on the activity of phagocytosing cells in human salmonellosis]

The functional activity of phagocytic cells in 52 salmonellosis patients was studied with regard to the following characteristics: percent share of phagocytosis, phagocytic index, nitro blue tetrazolium test results, digestive activity. In patients with the unfavorable course of salmonellosis (the formation of carrier state) disturbances in the bactericidal activity of neutrophils and monocytes were established. For 32 patients leukinferon was included in the complex of etiotropic and pathogenetic treatment. The preparation was introduced in 3 intramuscular injections of 10,000 I. U. at intervals of 48 hours (the course of treatment); 10 days after the last injection this course was repeated. The use of leukinferon restored the normal functioning of phagocytes and the number of T-lymphocytes.