Role of immune serum and complement in stimulation of the metabolic burst of human neutrophils by Plasmodium falciparum

Interaction between human neutrophils (polymorphonuclear leukocytes [PMN]) and Plasmodium falciparum in the natural defense of the host remains to be elucidated. In patients with acute malaria, oxygen consumption (QO2) of PMN at rest and after stimulation by zymosan was significantly increased compared with that in the controls. With 10% immune serum, both QO2 and chemiluminescence of normal PMN were significantly increased after stimulation by a P. falciparum erythrocyte culture. This activation was not observed with a nonparasitized erythrocyte culture and was correlated with parasitemia. Immune serum and complement were required to trigger this metabolic activation of normal PMN. With normal serum or heat-inactivated immune serum, a parasitized erythrocyte culture did not significantly stimulate QO2 or chemiluminescence of normal PMN. The classical complement pathway was essential for this stimulation, whereas the alternate pathway was less involved. Hyperimmune sera from subjects residing in endemic areas were more able to trigger the metabolic burst than were immune sera from subjects from other sources. The use of synchronous cultures showed that PMN were more stimulated by cultures rich in merozoites than by the same cultures which contained only intraerythrocytic forms. Giemsa staining showed granules of hemozoin and occasional merozoites or parasitized erythrocytes within PMN. This increase in production of activated oxygen radicals could damage intra-or extraphagocytic parasitic forms. As P. falciparum is sensitive to oxidant stress and PMN is the phagocyte with the most intense metabolic burst, the role of PMN in defense against malaria should be considered.     

Control of the Production of Oxygen Intermediates of Human Polymorphonuclear Leukocytes and Monocytes by B-Adrenergic Receptors

The control by R-adrenergic receptors of the production of oxygen radicals by zymosan-stimulated human polymorphonuclear leukocytes (PMN) and monocytes (Mψ) was studied in vitro by means of chemiluminescence. In addition we asked whether PMN Mpsi; exhibit differential sensitivity to β-adrenergic stimulation. Eor β-adrenergic stimulation we applied fenoterol ranging from 10^-9 to 10 M × 2.7. We found a dose-dependent suppression of the production of oxygen radicals, the ID50 being approximately 10^-6 M both for PMN and Mpsi;. By assessment of lactic dehydrogenase release a cytotoxic effect of the drug could be ruled out. When incubated together with the β-adrenergic antagonist propranolol at 10^-6 and 10^-7 M the suppressive effect of fenoterol could be reversed in dose-dependency. Preincubation with fenoterol revealed that the inhibitory action on Mpsi; persisted, in contrast, no such suppression could be verified with PMN. Our findings indicate the control of the production of oxygen intermediates of human PMN and Mpsi; by β-adrenergic stimulation. Furthermore, selective functional modulation of resting PMN and Mpsi; by β-adrenoceptors is suggested. These effects may be of importance in vivo, in particular since fenoterol was applied in pharmacological doses.     

Effects of nicotine on the functions of human polymorphonuclear leukocytes in vitro

Effects of nicotine on migration, extracellular release of lysosomal enzymes, and superoxide anion (O-2) production of human polymorphonuclear leukocytes (PMN) were studied. Nicotine (5 X 10(-6) to 5 X 10(-4) M) had no effect on random migration, chemotaxis to fMet-Leu-Phe, nor on chemokinesis induced by fMet-Leu-Phe. Nicotine, however, inhibited both extracellular release of lysosomal enzymes from PMN and O-2 production of PMN, both of which were induced by fMet-Leu-Phe and cytochalasin B. The inhibition of enzyme release and O-2 production by nicotine was not affected by atropine, hexamethonium, or acetyl beta-methylcholine, suggesting a direct action of nicotine on PMN functions. It is presumed that nicotine does not affect PMN migration to inflammatory sites, but inhibits the microbicidal functions of PMN. Exposure to PMN to nicotine introduced into the body by smoking could suppress their functions. This might result in harmful influences on the host defense mechanism, including antitumor function.     

Mannose inhibits the human neutrophil oxidative burst

Stimulated human neutrophils (PMNs) increase their oxygen consumption and secrete reactive oxygen species that are involved in bactericidal activity and inflammation. While studying lectin-mediated bacterial adherence, we observed that D-mannose appeared to inhibit PMN metabolism. Further studies showed that 100 mM mannose inhibited oxygen consumption by 82%, superoxide secretion by 84%, luminol-enhanced chemiluminescence (CL) by 98%, and hexose-monophosphate shunt activity by 100% when PMN were stimulated with 1 microM phorbol myristate acetate (PMA). Inhibition was also seen with 0.1 microM formyl-methionyl-leucyl-phenylalanine (fMLP), and 0.1 microM A23187, reagents thought to stimulate the respiratory burst by different transductional mechanisms. Inhibition was dose-responsive and specific since 100 mM D-galactose, alpha-D-glucose, or alpha-L-fucose only minimally affected PMN oxidative metabolism. Inhibition of PMA-induced superoxide production was seen almost immediately upon the addition of 50 mM mannose and was reversed by washing. Neutrophils remained viable as measured by trypan blue exclusion. These data suggest that mannose inhibits the neutrophil oxidative burst at the level of the hexose monophosphate shunt. Further investigation should elucidate the specific mechanism(s) of this burst inhibition as well as define uses for it as a tool to study oxidative as well as nonoxidative killing by PMN.     

Involvement of reactive oxygen metabolites in the candidacidal activity of human neutrophils stimulated by muramyl dipeptide or tumor necrosis factor

In the presence of the adjuvant glycopeptide muramyl dipeptide (MDP), purified human PMN exhibited an enhanced capacity to kill Candida albicans cells at various cell ratios. A significant effect was obtained at 100 ng/ml MDP, and the maximum was reached at 1 micrograms/ml MDP. Recombinant human tumor necrosis factor (rHuTNF), a monokine that enhances host resistance to bacterial and fungal infections, also stimulated the candidacidal potency of PMN with a maximal effect at 10(-2) ng/ml rHuTNF. When MDP- or rHuTNF-stimulated PMN were cultured with yeast cells, the intracellular production of oxygen metabolites was enhanced. Pretreatment with inhibitors of oxidative burst demonstrated that the yeast cell killing by MDP-stimulated PMN was not affected by SOD but was inhibited by sodium azide, indicating the involvement of myeloperoxidase (MPO)-halide system in fungicidal mechanisms induced by MDP. When PMN were stimulated with rHuTNF, the killing of yeast cells was neutralized by iodoacetamide, showing that the candidacidal potency of stimulated-PMN was due to oxygen derivatives. Inhibition by sodium azide and sodium benzoate indicated that these oxygen metabolites could be derived from the MPO-halide system but also from hydroxyl radical production. Moreover, SOD partially inhibited the fungicidal potency of rHuTNF-stimulated PMN, thus indicating a possible reutilization of the released O2- anion for intracellular killing. Cytochalasin B abrogated the PMN fungicidal potency in all cases.     

Control of the Production of Oxygen Intermediates of Human Polymorphonuclear Leukocytes and Monocytes by B-Adrenergic Receptors

Abstract

The control by R-adrenergic receptors of the production of oxygen radicals by zymosan-stimulated human polymorphonuclear leukocytes (PMN) and monocytes (Mψ) was studied in vitro by means of chemiluminescence. In addition we asked whether PMN Mpsi; exhibit differential sensitivity to β-adrenergic stimulation. Eor β-adrenergic stimulation we applied fenoterol ranging from 10^?9 to 10 M × 2.7. We found a dose-dependent suppression of the production of oxygen radicals, the ID50 being approximately 10^?6 M both for PMN and Mpsi;. By assessment of lactic dehydrogenase release a cytotoxic effect of the drug could be ruled out. When incubated together with the β-adrenergic antagonist propranolol at 10^?6 and 10^?7 M the suppressive effect of fenoterol could be reversed in dose-dependency. Preincubation with fenoterol revealed that the inhibitory action on Mpsi; persisted, in contrast, no such suppression could be verified with PMN. Our findings indicate the control of the production of oxygen intermediates of human PMN and Mpsi; by β-adrenergic stimulation. Furthermore, selective functional modulation of resting PMN and Mpsi; by β-adrenoceptors is suggested. These effects may be of importance in vivo, in particular since fenoterol was applied in pharmacological doses.     

Interactions between Human Polymorphonuclear Leukocytes and Influenza Virus

The effects of influenza virus A (H3N2) on several functions of human polymorphonuclear leukocytes (PMN) were examined. Incubation of PMN with virus induced chemiluminescence, aggregation, and degranulation of the leukocytes. The amount of chemiluminescence generated increased from 1 X 10(6) to 6 X 10(6) cpm when 2.5 X 10(6) to 2 X 10(7) virus particles were added to 2.5 X 10(6) PMN. Maximal aggregation occurred within 2 min and the response depended on the amount of virus added to the PMN. Release of acid phosphatase by virus-treated PMN was 62 +/- 12% within 1 h compared with 7 +/- 7% by control PMN (P less than 0.005). Incubation of PMN with influenza virus resulted in a diminished phagocytic activity of the phagocytes. PMN from a patient with chronic granulomatous disease were similarly affected. It was thus concluded that the observed defect in phagocytic activity was not due to the reactive oxygen species generated by the PMN during incubation with virus.     

The in vitro effects of mercury on peritoneal leukocytes (PMN and macrophages) from inbred brown Norway and Lewis rats.

The present paper demonstrates that HgCl2 can affect rat peritoneal polymorphonuclear leukocyte (PMN) and macrophage (M phi) functions in vitro. In addition, we have noticed that these effects of mercury vary according to the rat strain: for example, HgCl2 stimulates H2O2 release from Lewis (LEW) but not Brown Norway (BN) PMN. Similarly, LEW M phi produce high levels of H2O2 when exposed to HgCl2 in vitro, whereas BN M phi do not. Finally, mercury inhibits erythrophagocytosis of both LEW and BN "resident" peritoneal M phi. Preliminary experiments using M phi from other rat strains have also shown that MAXX M phi are stimulated by HgCl2 to release H2O2 in vitro, whereas Yoshida M phi are inhibited. Differences in lymphocyte responses (e.g. delayed-type hypersensitivity reactions and mitogen stimulation) between rats of various strains are well known. To these examples one may now add variations in PMN and M phi responses to mercury and possibly other metals. Our results suggest that caution should be exercised in interpreting the outcome of immunotoxicity studies in experimental animals. In particular, outbred rats may not provide appropriate models, that might be better obtained by comparative investigations of rats from various inbred strains.     

Neutrophil killing of two type 1 fimbria-bearing Escherichia coli strains: dependence on respiratory burst activation.

The production of reactive oxygen metabolites by neutrophils is thought to play a key role in host defense against invading microorganisms. In this study, the generation of oxygen metabolites induced by two uropathogenic Escherichia coli strains, ABU2 and PN7, and their subsequent killing in neutrophils were investigated. Both strains were grown to promote type 1 (mannose-sensitive) fimbria formation, but they differ with respect to other surface structures. When interacting with human neutrophils, the ABU2 bacteria adhered to and were phagocytized by the neutrophils, whereas PN7 bacteria adhered to the neutrophils but resisted phagocytosis. Both strains induced a pronounced neutrophil chemiluminescence response. However, when the intracellular and extracellular parts of the oxidative response were separated, we found that the predominant part of the response was of intracellular origin with the ABU2 bacteria as prey, whereas a large fraction of the response induced by the PN7 bacteria was extracellular. The general opinion is that production of reactive oxygen metabolites should be intraphagosomal to minimize the tissue-damaging effects of the metabolites and to optimize their bactericidal effects. However, since the surface-adherent bacteria (the PN7 cells) are killed in an aerobic but not an anaerobic milieu, whereas the ingested bacteria (the ABU2 cells) are killed in both aerobic and anaerobic milieu, we propose that extracellularly generated oxygen metabolites are of importance in killing E. coli strains that can resist neutrophil engulfment.     

N-acetylcysteine inhibits human neutrophil and monocyte chemotaxis and oxidative metabolism

The effect of N-acetylcysteine (NAC) on human neutrophil and monocyte cell viability, chemotaxis, oxygen consumption and chemiluminescence was studied. It was found that NAC at concentrations higher than 3 X 10(-2) M resulted in neutrophil and monocyte cytotoxicity. The studies on the effect of NAC on neutrophil and monocyte chemotaxis showed that NAC inhibited chemotaxis of both cell types in a concentration dependent manner. NAC at 3 X 10(-2) M inhibited chemotaxis of both cell types by about 50% and at 10(-1) M inhibited PMN chemotaxis by 95% and MNL chemotaxis by 85%. The studies on the effect of NAC on neutrophil chemiluminescence demonstrated that NAC at concentrations of 1.5 X 10(-2) M, or higher, inhibited the response of the activated cells totally. When pH adjusted NAC or Mucomyst was used the inhibition was observed with higher concentrations of the drug (1.5 X 10(-1) M). NAC exhibited a similar pattern of inhibition on monocyte chemiluminescence response. These findings demonstrate that NAC, at concentrations obtainable in vivo by inhalation, impairs the chemotaxis and generation of oxygen radicals by human phagocytic cells. This property of NAC could have important implications concerning the prevention of tissue damage caused by these cells in inflammatory areas.     

Differential generation of chemiluminescence — detectable oxygen radicals by normal polymorphonuclear leukocytes challenged with sera from systemic lupus erythematosus and rheumatoid arthritis patients

Summary The generation of chemiluminescence (CL)-detectable oxygen radicals by normal human polymorphonuclear leukocytes (PMN) after challenging with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) sera is described. CL was measured in a luminol-dependent assay and referred to a standard obtained when preformed immune complexes (Ic) (human tetanus toxoid-antitoxoid Ic resuspended in normal pooled serum) were tested on PMN. Normal sera gave rise to CL activity by PMN between 0% and 50% of the standard Ic (mean±standard error of the mean (SEM): 20.7±4.8). Sera from SLE and RA patients induced strikingly different biological effects on PMN. SLE sera generally induced a high CL-detectable generation of oxygen metabolites which may be causally related to the intense tissue damage (vasculitis) frequently observed in this disease. In contrast to SLE, RA sera induced a CL-detectable respiratory burst by PMN that was included in the normal range. Thus, the biological effects of these sera in terms of stimulation of toxic oxygen radical generation by phagocytes are quite different. This generation of oxygen radicals might reflect a different clearance of circulating Ic by PMN in SLE and RA disease.Abbreviations CL Chemiluminescence - PMN Polymorphonuclear Leukocytes - SLE Systemic Lupus Erythematosus - RA Rheumatoid Arthritis - Ic immune complexes - TAT tetanus-antitetanus toxoid - TAT-S tetanus-antitetanus toxoid resuspended in pooled, non-inactivated human serum - SEM standard error for the mean - EHM Eagle-Hepes-Medium - PBS phosphate-buffered-saline - RF rheumatoid factor - SPA staphylococcal protein A - ANA antinuclear antibodies - KD kilodaltons - Ag antigen     

Effect of ingested pentoxifylline on neutrophil superoxide anion production.

Superoxide and other oxygen radicals produced by activated polymorphonuclear leukocytes (PMN) may be important causes of tissue damage in a number of inflammatory conditions. Therefore, a drug which suppresses PMN responses in vivo is potentially important. In vitro, pentoxifylline (PTOX) inhibits superoxide anion production when PMN are stimulated with an activated complement component (C5a Des Arg) or formyl peptides but only at concentrations not achieved in the circulation. The aim of this study was to determine whether PTOX has an effect on PMN responses in vivo. Superoxide anion production, monitored by lucigenin-enhanced chemiluminescence, was inhibited by 40.5% +/- 8.0% (n = 8, P < 0.009) for C5a Des Arg and 47.7% +/- 9.6% (n = 8, P < 0.009) for formyl-methionylleucylphenylalanine stimulation 1.5 h after ingestion of 400 mg of PTOX in a slow-release tablet, with some inhibitory effects persisting at 5 h. There was a strong correlation between reduced PMN response to activated complement and plasma concentrations of three PTOX metabolites (P < 0.05), but not with plasma concentrations of the parent drug. In vitro investigations with each of the four methylxanthines showed two of these metabolites to be most effective at reducing PMN respiratory burst activity, lactoferrin release, and the expression of CD11b and CD18 molecules. Furthermore, this in vitro inhibitory activity was achieved at concentrations of metabolites achievable in vivo. The results suggest that PTOX reduces oxygen radical production and protects against unwanted tissue damage in vivo by the action of its metabolites.     

Oxygen-independent antimicrobial action in sphingosine-treated neutrophils

Sphingosine is reported to inhibit the oxidative burst and superoxide anion production of human polymorphonuclear neutrophils (PMN) phagocytosing in atmospheric oxygen (Wilson et al., 1986). We have confirmed its effect on superoxide production and examined the antimicrobial phagocytic capacity of PMN treated with sphingosine, comparing them with PMN, untreated but phagocytosing either under anaerobic conditions or in atmospheric oxygen. Sphingosine just like anaerobiosis partially inhibited, but did not eliminate, the bactericidal activity of PMN when compared to non-treated aerobic cells. In fact, sphingosine-treated PMN mimicked killing of Staphylococcus aureus (S. aureus) and Serratia marcescens (S. marcescens) due to anaerobic PMN. Moreover, our results with Salmonella typhimurium and sphingosine-treated cells duplicated results this laboratory published previously about comparative killing of Salmonella in aerobic versus anaerobic neutrophils. In these studies sphingosine-treated PMN took up bacteria as avidly as untreated PMN and retained their viability, as assessed by trypan blue exclusion. While sphingosine should not be completely substituted for anaerobic studies, it is a convenient screening reagent for the study of non-oxidative killing mechanisms of PMN. Results achieved with anaerobic and with sphingosine-treated cells suggest that O2-independent antimicrobial action is substantially more powerful than has been generally acknowledged.     

Hyperthermia-induced priming effect in neutrophil granulocytes]

BACKGROUND AND OBJECTIVE: Whole-body infrared-A irradiation (WBIAI) according to Ardenne is a newly developed version of hyperthermia. In clinical use benefits for patients with chronic infections have been reported. In order to find out more about the immunological background of the method we studied the question whether hyperthermia leads to priming effects in human polymorphonuclear leukocytes (PMN). MATERIAL AND METHODS: We therefore investigated the production of reactive oxygen radical species (ROS) measured by lucigenin-dependent chemiluminescence after stimulation with N-formylpeptide (FMLP, 10(-6) and 10(-7) M), C5a complement (10(-7) and 10(-8) M) or phorbolester (PMA, 10(-7) and 10(-8) M) in isolated PMN of 8 volunteers undergoding a 60-min hyperthermia treatment with the WBIAI. Blood was drawn 0/60/240/510 min after the start of hyperthermia treatment. In addition, we measured blood pressure, pulse, and temperature. RESULTS: In 5 cases a significant increase in ROS (p < 0.05) could be measured beginning 240 min after start of hyperthermia and further increasing until the 510-min time point. These results suggest a priming effect in PMN lasting far beyond the actual treatment period. The increase of ROS production following stimulation with FMLP, C5a or PMA was 60.4 +/- 21.6, 86.0 +/- 23.3, and 63.3 +/- 15.9% (SEM), respectively. Moreover, in all probands the maximal ROS production in PMN was observed 510 min after the beginning of WBIAI treatment. In 3 cases no difference in ROS could be observed. There was no difference in temperature, blood pressure, and pulse between responders and nonresponders. CONCLUSIONS: Our results show a hyperthermia-dependent priming effect of ROS production in PMN, suggesting an increase in immune reaction within the observation period of 510 min. Further investigations are necessary in order to specify responders and nonresponders and to characterize the results in specific diseases and the constitutions of the patients.     

Stereoselective Suppression of Neutrophil Function by Ketamine?

The effects of the commercially available ketamine preparation (Ketanest^TM). the ketamine racemate and of the two enantiomers, the R(-)-racemate and the S(+)-racemate, as well as its drug-free solvent were examined by N-formyl-methionyl-leucyl-phenylalanine-(FMLP)- and zymosan-induced oxygen radical production of polymorphonuclear cells (PMN). The racemate and the two enantiomers of ketamine suppressed FMLP- and zymosan-induced chemiluminescence of PMN in a dose-dependent fashion to the Same extent. Therefore suppression of chemiluminescence of PMN by ketamine does not result from a specific receptor interaction.     

Cytoskeletal changes as an early event in hydrogen peroxide-induced cell injury: a study in A549 cells.

Hydrogen peroxide (H2O2) and other oxygen metabolites have been implicated in the pathogenesis of cell and tissue injury. The nature of the injury occurring in cells exposed to oxygen metabolites is unknown. A549 cells, derived from human lung carcinoma, were exposed to glucose-glucose oxidase or hydrogen peroxide in vitro. The distribution of actin and cytokeratin filaments, as well as 51chromium (51Cr) release and trypan blue dye exclusion were assessed. Both glucose-glucose oxidase and H2O2 resulted in changes which were time- and dose-dependent. Alterations in the cytoskeleton were detected by immunofluorescence microscopy at two hours, at which time the cells excluded trypan blue dye, while 51Cr release and trypan blue uptake first occurred at 8 h and required a five-fold greater concentration of glucose oxidase. The addition of catalase to glucose-glucose oxidase or H2O2, or inactivation of glucose oxidase by boiling, abrogated the injury. Therefore, one of the early targets of H2O2-induced cell injury may be the cytoskeleton.     

Cytoskeletal changes as an early event in hydrogen peroxide-induced cell injury: a study in A549 cells

Hydrogen peroxide (H2O2) and other oxygen metabolites have been implicated in the pathogenesis of cell and tissue injury. The nature of the injury occurring in cells exposed to oxygen metabolites is unknown. A549 cells, derived from human lung carcinoma, were exposed to glucose-glucose oxidase or hydrogen peroxide in vitro. The distribution of actin and cytokeratin filaments, as well as 51chromium (51Cr) release and trypan blue dye exclusion were assessed. Both glucose-glucose oxidase and H2O2 resulted in changes which were time- and dose-dependent. Alterations in the cytoskeleton were detected by immunofluorescence microscopy at two hours, at which time the cells excluded trypan blue dye, while 51Cr release and trypan blue uptake first occurred at 8 h and required a five-fold greater concentration of glucose oxidase. The addition of catalase to glucose-glucose oxidase or H2O2, or inactivation of glucose oxidase by boiling, abrogated the injury. Therefore, one of the early targets of H2O2-induced cell injury may be the cytoskeleton.     

多形核白细胞在内毒素休克时肝组织损伤中的作用

家兔输注内毒素０．３ｍｇ／ｋｇ复制内毒素休克模型。输注４ｈｒ以后ＰＭＮ吞噬发光和Ｏ＾－２生成呈持续升高（Ｐ＜０．０５～０．０１），同时激活的ＰＭＮ释放氧自由基损伤肝细胞，引起肝细胞内ＭＤＡ含量和培养上清ＬＤＨ活性升高（Ｐ＞０．０５～０．０１）。体外内毒素与ＰＭＮ共孵，ＰＭＮ吞噬发光和Ｏ＾－２生成呈先升高后回降的变化，经内毒素在体外激活的ＰＭＮ也能明显引起肝细胞内ＭＤＡ含量和上清ＬＤＨ活性升高（Ｐ＜     

Prostasomes inhibit the NADPH oxidase activity of human neutrophils

Prostasomes are particular lipid vesicles secreted by the prostate in human semen and involved in several physiological functions such as the improvement of sperm motility or immunomodulation. We have previously shown that they reduced the overall reactive oxygen species (ROS) production of seminal polymorphonuclear neutrophils (PMN). The present study was conducted to define the mechanism by which prostasomes inhibit the ROS production of blood and seminal PMN. The luminol chemiluminescence measuring total ROS production of blood PMN stimulated by either a phorbol ester (PMA) or a chemoattractant peptide, formyl-Met-Leu-Phe (fMLP) was significantly inhibited by prostasomes. The NADPH oxidase activity of the PMN was measured by 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazo[1, 2-a]pyrazin-3-one (MCLA) chemiluminescence. Prostasomes inhibited the NADPH oxidase activity of blood or seminal PMN and increased the lag-phase of the enzyme after PMA stimulation. Prostasomes also inhibited significantly the NADPH oxidase activity of fMLP stimulated blood PMN, but the inhibition was not significant for seminal PMN. The lipid composition of blood PMN was analysed and compared to the lipid composition of prostasomes. This showed that prostasomes had a high cholesterol:phospholipid molar ratio and a high proportion of sphingomyelin. Together with the fact that prostasomes can rigidify the plasma membrane of blood PMN, these results led us to postulate that prostasomes inhibit the NADPH oxidase activity of PMN by lipid transfer from the prostasomes to the plasma membrane of the PMN.     

Comparison of Candida killing activity measured by chemiluminescence and cytomorphological methods in human phagocytes

Phagocyte function can be assayed by many laboratory tests including a cytomorphological method that uses Candida cells as target. The aim of this study was to correlate this technique with the production of toxic oxygen metabolites, measured by chemiluminescence (CL). The biological function of polymorphonuclear (PMN) cells and monocytes from the blood of 24 normal subjects and 25 patients with immunodeficiency diseases were studied. CL was measured using opsonized zymosan as the stimulating agent and, for the evaluation of Candida killing activity, C. pseudotropicalis and C. albicans were used as targets. A linear correlation between CL and lytic activity was observed with both PMN and monocytes from normal subjects and patients (r = 0.563 to 0.955; P less than 0.05 to less than 0.001). Our results indicate that the production of toxic oxygen metabolites, as measured by CL is closely related to the killing of Candida by PMN and monocytes.