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[Phagocytic link of immunity in patients surgically treated for chronic calculous cholecystitis].

Twenty-two females, 38 to 75 years of age, who underwent planned operation for chronic uncomplicated calculous cholecystitis were examined in the pre- and postoperative period. Postoperative pneumonia developed in 4 (13.4%) patients, no other complications occurred. Functional neutrophil activity was studied according to the following parameters: spontaneous and induced NBT test, myeloperoxidase activity, amount of cationic proteins, expression of Fc receptors, spontaneous and induced luminol-dependent chemiluminescence, neutrophil bactericidal action against H-thymidine-labelled Staphylococcus aureus (strain 209), amount of blood immunoglobulins, and the modulating effect of serum of patients on the chemiluminescence of neutrophils of healthy donors. The control group consisted of 35 volunteers whose ages ranged from 18 to 50 years. Basic differences were revealed between the indices of neutrophil activity in patients with an uneventful postoperative period and those of patients with infectious complications in the preoperative period which became much graver in the early postoperative period. This suggests that neutrophilic dysfunctions play a significant role in the development of postoperative infectious complications in this category of patients.

Adult↗

Folic acid deficiency and neutrophil dysfunction.

Polymorphonuclear leukocyte functions were studied in 92 patients with protein-calorie malnutrition. Serum folic acid levels were higher than 3 ng/ml in 38 patients and 3 ng/ml or less in 54 patients. Significant differences were found between these two groups of patients with regard to phagocytosis (81.5 +/- 1.9 versus 69.2 +/- 2.0 percent, p less than 0.001) and bactericidal ability (90.6 +/- 1.1 versus 84.5 +/- 2.3 percent, p less than 0.05). Correction of folic acid deficiency in 22 patients was associated with recovery of normal phagocytosis (p less than 0.001) but not bactericidal function. Adding folic acid to the serum of eight patients also restored normal phagocytic function (p less than 0.001). A correlation was found in vivo and in vitro between changes over time in folic acid levels and in phagocytosis.

Blood Bactericidal Activity↗

X-linked chronic granulomatous disease: report of one case.

Chronic granulomatous disease (CGD) is an inherited dysfunction of phagocytic cells secondary to a defect in the respiratory burst to kill catalase-positive microorganisms. This leads to recurrent life-threatening bacterial and fungal infections. We report a 1 year-10 month-old boy with X-linked CGD who was noted to have recurrent suppurative lymphadenitis since one and half month old. Failure to thrive, lymphadenitis and generalized skin lesions with multiple scar and dimples were found. Immunological data of patient, his mother and father were as follows: PMN phagocytosis (%): 98, 88, 92 (control, >80), PMN chemotaxis: 0.6, 1.0, 1.3 (control, >1.2), PMN bactericidal function test over a period of 2 hours (%): 28.1, 28.5, 84.8 (control, 82.1). PMN chemiluminescence (delta mV): 0.612, 364.1, 1131 (control, 614.1), H202 production (ug/mL): 1.6, 7.2, 16.8 (control, 14.1), NBT test: negative, mixed, positive (control, positive). His mother was a carrier. The patient expired with invasive salmonella infection before the availability of gamma-interferon prophylaxis.

Family Health↗

Immune impairment of alveolar macrophage phagocytosis during influenza virus pneumonia.

The pathogenesis of viral pneumonia is associated with an intact antiviral immune response. To determine the degree of involvement of the host response in influenza virus-induced impairment of pulmonary antibacterial defenses, mice were immunosuppressed by treatment with antilymphocyte serum (ALS). Eight days after infection, pulmonary defense mechanisms were quantitated by aerogenic challenge with Staphylococcus aureus; the ingestion of opsonized erythrocyte (EA) was used to monitor the phagocytic capability of alveolar macrophages obtained by pulmonary lavage. The ALS treatment alone caused no significant alteration in pulmonary antibacterial defenses or macrophage phagocytosis, nor did it interfere with viral multiplication. In noninfected lungs, less than 1% of the initial viable staphylococci remained viable at 24 h compared with proliferation to 490 +/- 147% in virus-infected lungs. Treatment with ALS prevented staphylococcal multiplication, the bactericidal value being 28 +/- 12% at the same time period. The phagocytic index (EA ingested/100 macrophages) in cells retrieved from normal lungs was 783 +/- 22 compared with 235 +/- 29 in macrophages from virus-infected lungs. The ALS ameliorated the impairment in phagocytic ingestion, the index being 505 +/- 34. Incubation of alveolar macrophages from virus-infected, ALS-treated animals with specific viral antibody reestablished the phagocytic defect in a dose-dependent manner; the index being 215 +/- 30 at the lowest dilution of antiviral globulin. The data demonstrate that the virus-induced suppression of pulmonary antibacterial defenses caused by dysfunction in alveolar macrophage phagocytosis is, in part, immunologically mediated.

Animals↗

Phagocytosis and neutrophil bactericidal capacity in patients with uremia.

The phagocytic activity and bactericidal capacity of polymorphonuclear neutrophils (PMN) were evaluated in patients with advanced chronic renal failure. The studies were made in patients undergoing hemodialysis, maintenance peritoneal dialysis as well as in nondialysed patients. Evaluations were carried out by using of the recently described fluorochrome microassay which enabled these parameters to be estimate independently. The phagocytic activity was seriously diminished in nondialysed patients, whereas it was similar to controls in those hemodialysed and undergoing peritoneal dialysis patients. In all evaluated groups of patients the bactericidal capacity was significantly reduced. The lowest values could always be observed in nondialysed patients. The decrease of bactericidal capacity was significantly more evident in patients undergoing peritoneal dialysis as compared with those hemodialysed. The obtained results confirm some previous reports suggesting the impairment of PMN function in uremic patients. This results in their increased susceptibility to infection. They also reveal the existence of a close relationship between the extent of observed dysfunctions and the management applied.

Bacterial Infections↗

Alterations of bacterial clearance induced by propofol.

BACKGROUND: The purpose of the study was to investigate the potential influence of the anaesthetic agent propofol on immune function in terms of systemic clearance and organ distribution of injected Escherichia coli in a rabbit model. METHODS: Defined numbers of E. coli (1.3 x 10(8) colony-forming units, CFU) were injected intravenously 1 h after starting a 4-h infusion of the anaesthetic propofol (2 ml.kg-1.h-1, Disoprivan 1%; n = 6)) or after saline application (n = 6). As propofol is formulated in a 10% lipid emulsion, the lipid vehicle Intralipid (2 ml.kg-1.h-1; n = 6) alone was investigated in a separate group. Parameters monitored were arterial pressure and rates of bacterial elimination from the blood. Three hours after bacterial injection, the animals were killed, and tissue samples of liver, spleen, lung, and kidney were collected for microbiological examinations. RESULTS: Compared to saline-treated animals, infusion of propofol induced increased accumulation of E. coli in lung and spleen, thus reflecting reticuloendothelial system dysfunction. CONCLUSION: As the lipid emulsion by itself induced the same effects, the impaired immune function due to propofol is thought to be attributed to its solvent Intralipid.

Anesthetics, Intravenous↗

Papillon-Lefèvre syndrome: neutrophil function in 15 cases fron 4 families in Egypt.

OBJECTIVE: The primary purpose of this study was to investigate the periodontal pathologic cause of Papillon-Lefèvre syndrome by comparing, with respect to neutrophil function, probands with Papillon-Lefèvre syndrome from 4 families in Egypt, unaffected siblings of the probands, and age-matched and gender-matched control subjects. STUDY DESIGN: Family histories and clinical dermal and oral manifestations of Papillon-Lefèvre syndrome were evaluated for 15 affected members of 4 families with the syndrome, 10 siblings of the probands, and 7 age-matched and gender-matched controls. Phagocytic and intracellular killing (lytic activity) of polymorphonuclear neutrophils was evaluated for all subjects according to a modification of the method of Wilkinson; opsonization was evaluated according to a modification of the methods of Cutler et al. Data were analyzed by means of analysis of variance. RESULTS: Family pedigrees were plotted, and consanguinity was noted in 3 of the 4 families with Papillon-Lefèvre syndrome. The means and SDs for phagocytic killing, lytic activity, and opsonization indices were as follows: probands, 4.76+/-1.99, 0.42+/-0.20, and 0.84+/-0.07; unaffected siblings, 10.4+/-1.3, 3.3+/-0.3, and 0.84+/-0.07; controls, 10.8+/-0.8, 3.5+/-0.6, and 0.85+/-0.05. The phagocytic killing and lytic activity indices demonstrated significance between the probands and both siblings and controls (P<.0005), whereas the opsonization index did not demonstrate significance between groups. CONCLUSIONS: Significantly decreased neutrophil function in probands with Papillon-Lefèvre syndrome was demonstrated with respect to neutrophil phagocytotic and lytic activity but not with respect to opsonization. Therefore, specific neutrophil dysfunction appears to be etiologically involved in this disorder.

Adolescent↗

Neutrophil function in gram-negative rod bacteremia. The interaction between phagocytic cells, infecting organisms, and humoral factors.

To assess the phagocytic and bactericidal function of neutrophils in the acute stages of gram-negative rod bacteremia, cells from 30 nonleukopenic patients were studied in a test system utilizing plasma obtained simultaneously with culture-positive blood, the autologous infecting strain, and two laboratory test strains of Staphylococcus aureus and Pseudomonas aeruginosa. Results were compared to those obtained with normal neutrophils and plasma. Patient and control plasma were simultaneously tested with each source of phagocytic cells to localize any abnormalities. Four patients had a defect against their infecting strain, 33% of the inoculum phagocytized and killed versus 80% by controls. In these cases differences were localized to the patients' plasma, as normal plasma tested with patients' cells reversed the defect. Thus, four patients had impaired opsonization when compared to normal controls, but we also observed that 11 of 30 bacteremic isolates, all Escherichia coli, showed absolute or relative resistance to phagocytosis in the patient and control assay system. No intrinsic granulocyte killing abnormalities were noted. There was poor correlation between results obtained with infecting strains compared to laboratory test organisms. We conclude that in patients without evidence of an inherited neutrophil bactericidal disorder, recurrent infection, or treatment with cytotoxic drugs, intrinsic bactericidal defects are uncommon at the onset of gram-negative bacteremia, and impaired opsonization is the most commonly encountered cause of neutrophil dysfunction.

Blood Bactericidal Activity↗

Use of physical chemistry and in vivo exposure to investigate the toxicity of formaldehyde bound to carbonaceous particles in the murine lung.

Knowledge about the health effects of exposure to formaldehyde associated with automotive emissions is of pivotal importance in the risk assessment of this agent. Mobile sources emit many combustion-derived pollutants, including formaldehyde, in association with respirable carbon particles. Because it is hydrophilic, most of the inhaled formaldehyde is absorbed in the upper respiratory tract. However, if the organic vapor is adsorbed on respirable particles, formaldehyde may be deposited in the deep lung with the inhaled particles and may be available to interact adversely with cells along the lung parenchyma. On the respiratory surface, the alveolar macrophage phagocytic system plays the pivotal role in defending the lung against infectious agents. Susceptibility to respiratory infections is a relevant and sensitive indicator of the adverse effects of air pollution because acute and chronic exposures to a variety of air pollutants have been shown to decrease pulmonary antibacterial defenses. The goal of this research was to investigate whether exposure to formaldehyde decreases resistance to respiratory infections through dysfunctions of the alveolar macrophage phagocytic system. The study also explored whether interactions between formaldehyde and respirable carbon black particles alter susceptibility to respiratory infections and impairment of alveolar macrophage phagocytosis by delivering adsorbed formaldehyde to the deep lung with the inhaled particles. A carbon black, Regal GR, was used in these studies as a surrogate for the carbonaceous core of Diesel particulate matter. This material was selected to represent the worst-case scenario because the carbon black was expected to adsorb formaldehyde strongly. To accomplish this goal, mice were exposed to formaldehyde and to carbon black and formaldehyde combinations; increased susceptibility to respiratory infections was quantified by alveolar macrophage-dependent intrapulmonary killing of Staphylococcus aureus after an inhalation challenge with the bacterium. The salient findings of the bactericidal studies are as follows: Fifteen parts per million (ppm)* formaldehyde impaired the intrapulmonary killing of S. aureus when exposure followed the bacterial challenge. One ppm formaldehyde impaired the intrapulmonary killing of S. aureus when exposure preceded and was continued after the bacterial challenge. Coexposures to target concentrations of 3.5 mg/m3 carbon black and 2.5 ppm formaldehyde, or 10 mg/m3 carbon black and 5 ppm formaldehyde after the bacterial challenge had no effect on the intrapulmonary killing of S. aureus. Preexposure for four hours per day for four days to target concentrations of 3.5 mg/m3 carbon black and 2.5 ppm formaldehyde had no effect on the intrapulmonary killing of S. aureus when the assay was performed one day after the cessation of exposure.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Concurrent estimation of the kinetics of adhesion and ingestion of Staphylococcus aureus by human polymorphonuclear leukocytes (PMNs).

Direct recording of the kinetics of early phagocytic events, recognition or adhesion and ingestion, may better characterize some forms of polymorphonuclear leukocyte (PMN) dysfunction. This report describes a method and criteria to discriminate concurrently between adhesion and ingestion of Staphylococcus aureus by human PMNs at the level of the light microscope. The criteria were confirmed by several lines of direct evidence: low temperature and cytochalasin b treatment of PMNs; lysostaphin digestion of target Staphylococcus aureus after PMN incubation; and differential ingestibility of colony types I and III N. gonorrheae. Concurrent determinations of the initial kinetics of adhesion and ingestion of bacteria by PMNs demonstrated generalized first order kinetics, sensitive to bacterial challenge ratio and total particle density. Most importantly, the method may be applied to determine if phagocytically defective PMNs actually fail to recognize opsonized bacteria.

Blood Bactericidal Activity↗

Protection of erdosteine on smoke-induced peripheral neutrophil dysfunction both in healthy and in bronchitic smokers.

The purpose of the present study was to determine whether erdosteine and its metabolites (substances containing thiol groups) can prevent the alteration of the chemotactic function of polymorphonuclear cells (PMN) from peripheral blood induced by cigarette smoke of eight healthy non-smoking volunteers, when incubated in vitro before smoke exposure, and whether oral treatment with erdosteine (900 mg/day) for two weeks might restore the chemotaxis of PMN, either from eight healthy or from 16 chronic bronchitic smokers. The chemotactic stimuli in vitro were casein, lipopolysaccharides (LPS), and formyl-methionyl-leucyl-phenyalanine (FMLP). The results of the study in vitro have confirmed that PMN from non-smoking volunteers shows a reduced chemotactic responsiveness when exposed in vitro to smoke. This can be partially prevented in a dose-related manner by pre-incubation with erdosteine, its metabolites, cysteine, and glutathione (metabolites I and II being at least 10 times more active than the intact substance and the known biological standards also containing thiol groups). The experiment on PMN from healthy smokers (in a double-blind crossover design versus placebo) has indicated that the chemotaxis can be improved only after treatment with erdosteine. The same observation has been made in the experiment on PMN from smokers affected by chronic bronchitis (in a double-blind design versus placebo with two distinct groups). In these patients the phagocytic and bactericidal activities of PMN were not affected by the smoke and therefore, neither one was influenced by erdosteine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Defects in the oxidative killing of microorganisms by phagocytic leukocytes.

One of the most important mechanisms of phagocytic killing of ingested microorganisms by leukocytes is the generation of toxic oxygen products. During phagocytosis, neutrophils, as well as monocytes and macrophages, display a strongly increased cell respiration. Quantitatively the most important product of this reaction is hydrogen peroxide. Superoxide is also generated in large amounts, probably as an intermediate in the formation of hydrogen peroxide. Indications exist that singlet oxygen and hydroxyl radicals are also formed in this process. Some of these oxygen products have microbicidal properties by themselves. The effect of hydrogen peroxide is greatly enhanced by the enzyme myeloperoxidase. Several dysfunctions of this sytem are known. In chronic granulomatous disease the enzyme system that produces superoxide is not operative. Thus, no superoxide or hydrogen peroxide is generated, leading to a severely decreased bacterial killing capacity. The exact molecular defects in the X-linked and the autosomal form are as yet undefined. Two variants are also known: lipochrome histiocytosis, with different clinical and histological manifestations, and a 'triggering defect' where only strongly opsonized particles trigger the respiratory burst. Myeloperoxidase deficiency leads to slightly decreased killing capacity, especially for yeasts. In glucose-6-phosphate dehydrogenase deficiency no oxygen radicals or hydrogen peroxide are produced because no equivalents for oxygen reduction can be generated in the hexose-monophosphate shunt. Deficiencies in the glutathione redox system also result in impaired phagocyte function, probably because the cells have to be protected against their own toxic oxygen products.

Blood Bactericidal Activity↗

Leukocyte phagocytic function and dysfunction.

Although some species of bacteria are killed in vitro by humoral factors in cell-free serum, the in vivo experience with leukopenic patients illustrates the critical role played by phagocytic leukocytes in host resistance to infection. Effective ingestion and killing of micro-organisms requires the sequential and integrated function of the elements of the phagocytic system. Each step in the phagocytic process is also a potential crack in the armor of host defense, and an increasing number of clinically significant disorders of phagocytic function are being recognized and described (5). The phagocytic leukocytes are equipped with a variety of intracellular microbicidal mechanisms which provide a degree of overkill capacity and allow these cells to meet the challenges posed by the many and varied microbial transfressors. Undoubtedly, other phagocytic disorders will be discovered and other important aspects of the intraleukocyte killing mechanisms will be elucidated. For instance, little is known about the function of leukocytes within the relatively hypoxic environment of injured tissue where so many bacterial infections begin. As our understanding of phagocytic function develops, new ways may be found to augment host resistance by preservation or stimulation of the phagocytes.

Animals↗

Pseudomonas aeruginosa: quantitation of maximum phagocytic and bactericidal capabilities of normal human granulocytes.

The maximum phagocytic and bactericidal capabilities of normal human PMNs against a seroresistant strain of Pseudomonas aeruginosa were evaluated by morphological observation, uptake of radiolabeled bacteria, and quantitative killing methods. The number of bacteria killed per PMN increased from 3 to 23 as the bacteria-to-PMN ratio was increased from 3:1 to 100:1. Conversely, the percent of bacteria killed decreased from 94% to 3%. In monolayers, an increase in the inoculum from 10(5) to 10(8) cfu/ml was associated with greater phagocytosis and a sixfold increase in PMNs containing greater than or equal to 5 bacteria/PMN. With the use of 75Se-labeled P. aeruginosa, optimal phagocytosis was observed with 10 to 20 bacteria/PMN in 20% NPS. Maximum uptake of 70% occurred in 40 min. No difference was observed in the uptakes of live or heat-killed bacteria. The maximum number of bacteria ingested per PMN was 32 +/- 5 at the highest ratio tested (100:1). The use of altered opsonic sources indicated the need for the classical complement pathway for optimal phagocytosis. Thus study describes the requirements and necessary standardization parameters that were found to be essential for a highly reproducible method for measuring phagocytosis and killing of P. aeruginosa by normal human PMNs. This method could be employed for clinical assessment of partial opsonic or PMN dysfunction in the study of the interaction of PMNs and P. aeruginosa.

Blood Physiological Phenomena↗

Neutrophils and host defense.

Neutrophils, the predominant phagocytes of circulating blood, are the first cells to arrive at sites of infection. Although neutropenia has long been recognized to predispose to infection, recently other syndromes marked by frequent infections have been shown to be caused by an underlying neutrophil dysfunction. Efforts to define the molecular pathology of such disorders have helped delineate the molecular basis of normal neutrophil function. Advances have been made in defining the roles of the neutrophil's varied receptors in recognition, movement, and adhesive phenomena. Progress in establishing the pathogenesis of chronic granulomatous disease has provided important insights into the enzymatic machinery that normal neutrophils use to produce antimicrobial oxidants. The identification and precise characterization of antimicrobial components, such as defensins, have outlined the potential roles of "natural antibiotics" in neutrophil-mediated host-defense functions. These areas of neutrophil function will be reviewed and placed in a clinical context to guide physicians in evaluating children and adults with frequent or unusual infections.

Blood Bactericidal Activity↗

[Reduced phagocytic capacity of circulating granulocytes in diabetes mellitus].

Impaired PMN function is regarded as a major cause for infectious complications in diabetes mellitus (d.m.). The aim of this study was to investigate the phagocytic PMN functions "ingestion" (IN) and "bacterial killing" (BK) with regard to metabolic control parameters and influences of variable glucose concentrations on these PMN functions in vitro. Our findings demonstrated a significant reduction of IN and BK in diabetic subjects compared to controls (p less than 0.001 resp.). The differences between type I and type II d.m. did not reach statistical significance. Linear regression analysis showed significantly negative correlations for fasting blood-glucose concentrations as well as glycosylated hemoglobin (HbA1) and IN (r = -0.34, p 0.03; r = -0.67, p = 0.001) and a highly positive for BK (r = 0.73, p = 0.0001). In vitro there was a significant decrease in IN and BK both in diabetic subjects and controls for glucose concentrations greater than 27.7 mmol/l (p = 0.01 resp.). These data clearly demonstrated impaired PMN ingestion and bacterial killing in diabetic patients, and the degree of PMN dysfunction is inversely related to the degree of metabolic control of diabetes. These findings suggest inhibitory effects of hyperglycemia on PMN functions, thus contributing at least partly to altered host defense in diabetes mellitus.

Blood Bactericidal Activity↗

Aspects of leukocyte function and the complement system following aerobic exercise in young female gymnasts.

Recent studies have reported reduced immunity in trained athletes. Scant information exists on changes in the immune function among trained children. The purpose of this study was to assess the effect of aerobic exercise on the phagocytic process of neutrophils and the complement system in young athletes. Subjects included prepubertal elite female gymnasts (n = 7) and untrained girls (n = 6) aged 10-12 years. Venous blood was withdrawn before, immediately post and 24 h following a 20-min run at a heart rate of 170-180 beats.min-1. Neutrophil random migration, chemotactic activity, bactericidal function and PMA/FMLP-stimulated superoxide anion release as well as various complement components were assessed. Net chemotaxis was found reduced (P < 0.05) 24 h following exercise (58 +/- 11 vs. 36 +/- 11 cells/field in gymnasts and 47 +/- 7 vs. 42 +/- 8 cells/field in untrained girls pre- and 24 h post-exercise, respectively). The basal values, as well as post-exercise values of bactericidal activity were lower (P < 0.05) in gymnasts as compared with the control group (0.8 +/- 0.3, 0.8 +/- 0.2 and 0.8 +/- 0.1 log decrease of colonies in gymnasts at pre-, immediately post-, and 24 h post-exercise, respectively and 1.1 +/- 0.1, 1.1 +/- 0.1 and 1.0 +/- 0.2 log decrease of colonies in controls, respectively). No significant effect on the bactericidal activity was observed in either group following exercise. The addition of homologous sera did not correct the bactericidal activity. PMA-stimulated superoxide anion release decreased (P < 0.05) among gymnasts immediately following exercise (5.7 +/- 0.4 vs. 4.4 +/- 1.0 mmol O2/10(6) PMN.min) and remained low 24 h later. The same trend was observed in FMLP-stimulated neutrophils but the data were not significant. Significantly decreased levels (P < 0.05) of the early complement components (C1Q, C1R) were also found following exercise (1.34 +/- 0.64 vs. 1.27 +/- 0.28 and 1.09 +/- 0.07 vs. 1.02 +/- 0.06 pre- and post-exercise in gymnasts and untrained, respectively). Furthermore, consistently lower C2 and C3 were observed in gymnasts compared with controls. Neutrophil dysfunction as well as impairment of the complement system seem to occur following exercise.

Analysis of Variance↗