Niveles séricos de cinc y cobre y funciones leucocitarias en pacientes diabéticos / Zinc and copper serum levels and leukocyte function in diabetic patients

Fueron estudiadas 96 muestras, divididas en tres grupos para su estudio. Los grupos uno y dos correspondían a pacientes diabéticos ingresados en la institución clasificados en anérgicos y reactivos, de acuerdo, con la respuesta dada a las pruebas dérmicas de hipersensibilidad retardada. El grupo tres estaba compuesto por sujetos supuestamente sanos, procedentes del Banco de Sangre del Hospital "Salvador Allende". Fueron determinadas las pruebas dérmicas, concentración sérica de cinc y cobre, opsonización, adherencia leucocitaria y actividad fagocítica y microbicida. Diferencias estadísticamente significativas fueron encontradas para la concentración sérica de cinc, actividad fagocítica y microbicida entre los grupos anérgico-reactivo, anérgico-control y reactivo-control. Una asociación negativa fue encontrada entre la edad y estas variables, que mostraron diferencias. Por lo tanto, los diabéticos tienen una disminuida capacidad de defensa leucocitaria, más pronunciada en los pacientes anérgicos. Este descenso está en releción inversa con la edad

Inhibition of polymorphonuclear leukocyte respiratory burst by elevated glucose concentrations in vitro.

Although impaired polymorphonuclear leukocyte (PMN) function may be a cause of infectious complications in diabetic patients, the mechanisms of altered cell function are not understood. Our studies of PMN function in healthy subjects demonstrated significant reduction in the respiratory burst after 30 min of in vitro cell exposure to glucose concentrations greater than 11 mM (200 mg/dl). The respiratory burst was reduced 28 +/- 5 and 74 +/- 7% in PMNs incubated with 11 and 56 mM glucose, respectively. The impairment was independent of the cell stimulus (chemotactic peptide, calcium ionophore, or phorbol ester) and was not affected by sorbinil or myo-inositol. Because both D- and L-glucose had similar inhibitory effects, a nonenzymatic mechanism appeared to be the cause of impaired PMN function. Although mannitol and sorbitol did not affect cell function, monosaccharides (glucose, mannose, fructose) that form Schiff-base adducts with protein inhibited PMN function. These findings suggest a potential role for protein glycosylation in glucose-induced impairment of PMN function.

Thermal regulation of FMLP receptors on human neutrophils.

Polymorphonuclear leukocytes (PMNs) from subjects diagnosed as having juvenile periodontitis (JP) have been categorized on the basis of their chemotactic (CTX) response to f-met-leu-phe (FMLP) when assayed concurrently with PMNs from periodontally healthy subjects (HP). When PMNs from JP groups demonstrating depressed CTX were assayed for lysosomal enzyme secretion (LES) in response to FMLP, there were no significant differences with respect to rate or amount. Significant differences were observed between HP and chemotactically depressed JP cells when assessed for FMLP receptor ligand binding at 23 degrees C, but not at 4 degrees C. Receptor differences observed at 23 degrees C in HP cells included an increase in amount of total binding, number of receptors, and available displaceable binding sites, compared with the chemotactically depressed JP PMNs, whereas the receptor affinities were similar. These data suggest that differences in FMLP receptor density in JP PMN that are chemotactically depressed may be related to processes that modulate receptor mobility and/or expression.

Función fagocítica de los leucocitos polimorfonucleares neutrófilos (PMN) en pacientes hemofílicos / Phagocytic function of neutrophilic polymorphonuclear leukocytes (NPM) in hemophilic patients

Se estudió la función fagocitíca de los leucocitos polimorfonucleares neutrófilos (PMN) en un grupo de 25 pacientes hemofílicos con edades comprendidas entre 10 y 58 años. Todos los pacientes recibieron tratamiento con crioprecipitado. Los resultados de la ingestiòn y opsonización no presentaron diferencias estadísticamente significativas al compararlos con el grupo control: sin embargo, el porcentaje de PMN adherentes en los pacientes hemofílicos resultó significativamente elevado (pacientes 95,7% + 1,96; controles 88,7 + 5,35%)

Immune cellular interactions during sepsis and septic injury.

The cellular activity generated by PMNs and macrophages in association with diverse cytokines has a profound impact on all major functional responses of host cellular components during sepsis and septic injury. It is the modulation of these cellular interactions and their effect on the continuum between appropriate and inappropriate responses during inflammation that will dictate the outcome of humans with sepsis.

Polymorphonuclear leucocyte motility in men with ankylosing spondylitis.

The polymorphonuclear leucocyte (PMN) response to a chemotactic or chemokinetic stimulus is enhanced in men with ankylosing spondylitis (AS). This effect does not parallel the severity of disease activity or the size of the acute phase response, and it is independent of non-steroidal anti-inflammatory drug treatment. Polymorph function is normal in HLA-B27 positive brothers of probands with AS and in other HLA-B27 positive individuals in the absence of disease. Polymorph motility is also normal in patients with psoriasis vulgaris or Crohn's disease, indicating that enhanced PMN motility is not a non-specific consequence of all inflammatory disorders.

Estudio de la capacidad fagocítica del granulocito neutrófilo en niños deficientes de hierro / Study of phagocytic capacity of neutrophil granulocyte in iron deficient children

Se estudió la capacidad fagocítica del granulocito neutrófilo (GN) en 44 niños de Ciudad de La Habana, de ambos sexos, con edades comprendidas entre 6 y 18 meses; la mitad de estos niños presentaron deficiencias de hierro y el resto tuvo valores normales. La capacidad fagocítica resultó similiar, tanto para los deficientes de hierro, como para los normales. No se encontró correlación estadística entre la hemoglobina, índice de saturación, protoporfirina, ferritina, grado de deficiencia de hierro y la capacidad de ingestión del GN. Estos resultados concuerdan con las comunicaciones de otros autores

A study of the functions of polymorphonuclear neutrophil in patients with Down's syndrome.

Patients with Down's syndrome (DS) are predisposed to infectious diseases, particularly of the respiratory tract. Together with the occurrence of cardiac defects, this is one of the main determinants of their life expectancy. The aim of the present work was to study a series of immunological parameters that would allow us to evaluate the functional behaviour of the neutrophil polymorphonuclears of the patients with trisomy 21 and the possible relationship between this and the susceptibility of this kind of patient to such infections. The results obtained point a significant decrease (p less than 0.001) in the adhesiveness index and in the two indexes relating to the evaluation of random mobilities of cells ("leading front" and "lower face of filter"). Although the neutrophil chemotactic responsiveness of these patients is decreased with any of the attractants employed (casein and activated sera), the differences observed with respect to the control population are more patent upon analyzing the function on the "lower face of filter". Study of phagocytosis of Candida albicans and candidicidal activity of PMN reveals a normal behaviour in the presence of autologous (patient) and heterologous (control) serum. We propose that the alterations found in the PMN cell functions of DS patients could be due to intrinsic cellular defects and that this would help to explain why such patients tend to undergo repetitive infective processes.

Abnormal rabbit heterophil chemotaxis following thermal injury. An in vivo model of an abnormality of the chemoattractant receptor for f-met-leu-phe.

Previous studies have shown that the decreased neutrophil migratory responsiveness seen in burned patients correlates with the extent of thermal injury and the extent of the neutrophil-specific granule deficiency. To understand better the relationship between the neutrophil dysfunction, degranulation, and thermal injury, a rabbit model was studied. Eighteen rabbits were burned over 20% of their surface area. Assay of peripheral blood heterophils disclosed decreased migratory activity compared with preburn levels and decreased lysozyme content vs preburn levels, but no change in the beta-glucuronidase content. The specific binding of tritiated formyl-methionyl-leucyl-phenylalanine to peripheral blood heterophils was increased fivefold over that of control cells. These studies indicate that, following thermal injury, there is a selective decrease of specific granule contents and an increase in chemoattractant binding to the cell and also suggest an abnormality in chemoattractant receptor processing. The rabbit provides a convenient model for the study of compromised host defenses following thermal injury.

Lactoferrin, myeloperoxidase, lysozyme and eosinophil cationic protein in exudate in delayed type hypersensitivity.

A skin window technique was used to study the morphology of leucocytes in upper dermis and exudate during nickel challenge in patients with contact allergy to nickel. Contact allergic patients and healthy volunteers tested with a skin widow without addition of nickel to the chamber medium served as controls. The morphology of the leucocytes in dermis was studied in biopsies taken 8, 24, or 48 h after skin window application, and in a parallel test the morphology of the exudate was examined by sequential collection of the chamber medium during a 48 h period. The infiltrate in dermis of contact allergic patients with nickel challenge in the chamber medium showed a time-dependent increase of mononuclear cells, eosinophils and basophils and a concomitant decrease of polymorphonuclear granulocytes, characteristic of a combined specific and unspecific inflammation. The morphology of the exudate in contact allergic patients exposed to nickel showed a dominance of polymorphonuclear granulocytes throughout the study period, while mononuclear cells, eosinophils and basophils were detected at a much lower quantity and with a considerable delay. Further, we studied the kinetics of the leucocyte granule proteins: lactoferrin, myeloperoxidase, lysozyme and eosinophil cationic protein in exudate fluid in a parallel test. A significant higher flux was found for all during the second day of allergen exposure compared to contact allergic patients without allergen challenge as well as normal volunteers. The increased protein fluxes were not accompanied by an increased flux of polymorphonuclear granulocytes in the exudate.(ABSTRACT TRUNCATED AT 250 WORDS)

Experimental murine schistosomiasis mansoni: inhibition of neutrophil granulocyte inflammatory reaction.

1. The mobilization of neutrophils into the peritoneal cavity following stimulation with sterile mineral oil was studied in normal and schistosome-infected mice. This response was correlated with changes in blood neutrophil counts and with the production and release of medullar granulocytes. 2. The peritoneal neutrophil inflammatory reaction was considerably reduced in schistosome-infected mice. The medullar pool of mature neutrophils was totally depleted, in spite of an increased number of immature neutrophil precursors. 3. We conclude that the decreased inflammatory response of neutrophils during schistosomiasis is due to the delay of their maturation in the bone marrow. A similar delay has been observed in schistosomal patients. A causal relationship between delay of neutrophil maturation and sensitivity of schistosomal patients to chronic microbial infections is suggested by these data.

Function of exudate neutrophils from skin in psoriasis.

Human neutrophils harvested from skin chambers containing autologous serum in psoriatic patients were compared with peripheral blood neutrophils by examining migration, phagocytosis, and oxidative activation. Random migration was reduced in exudate cells, whereas the chemotactic response to yeast-activated serum was evident not only in blood neutrophils, but also in exudate cells. The metabolic activation of exudate neutrophils, when stimulated with formyl-methionyl-leucyl-phenylalanine and measured as chemiluminescence, was enhanced by 50-400% compared to blood neutrophils. The chemiluminescence response to phorbol myristate acetate was on the other hand reduced to 35%. In the phagocytic assay, using C3bi- and IgG-opsonized yeast particles, exudate neutrophils from non-psoriatic healthy controls showed enhanced uptake of C3bi-coated yeast compared to blood neutrophils. In psoriatics, the blood neutrophils showed enhanced C3bi-mediated phagocytosis compared to non-psoriatic control cells. No further increase in C3bi-mediated phagocytosis was then seen in exudate cells from these patients. IgG-mediated phagocytosis was in contrast to C3bi similar between blood and exudate neutrophils in psoriatics and non-psoriatic controls. These experiments show that during exudation priming of different receptor-mediated processes can occur. However, no significant difference was observed between different functional capacities in exudate neutrophils from psoriasis patients and non-psoriatic controls.

Elevated phagocytosis, oxidative burst, and F-actin formation in PMNs from individuals with intraoral manifestations of HIV infection.

Alterations in polymorphonuclear leucocyte (PMN) function are frequently associated with intraoral disease. The purpose of this study was to evaluate if alterations exist in three early stimulatory events of PMN function in individuals with intraoral manifestations of human immunodeficiency virus (HIV) infection. Peripheral PMNs were isolated from nine HIV-seropositive male homosexuals with HIV-associated periodontitis and intraoral candidiasis and healthy HIV-seronegative age-matched heterosexuals (controls). Phagocytosis was assessed using fluorescent microspheres, oxidative burst was assessed via hydrolysis of 2',7'-dichlorofluorescein (FCDH) to 2',7'-dichlorofluorescein (FCDA) with PMA stimulation, and F-actin formation was assessed with NBD-phallacidin stain after stimulation with f-Met-Leu-Phe. Compared to controls, seven of nine HIV-seropositive patients demonstrated a significant increase in the percentage of phagocytic cells while seven of nine HIV-seropositive patients demonstrated a 5-59% increase in number of beads per cell. In the oxidative burst assay, seven of seven HIV-seropositive patients demonstrated a significant increase over controls in FCDA stain with PMA stimulation. In the F-actin assay, four of five HIV-seropositive patients demonstrated a significant increase over controls in NBD-phallacidin staining after f-Met-Leu-Phe stimulation.

Acute cigarette smoke exposure in dogs: the inflammatory response.

Acute cigarette smoke causes polymorphonuclear leukocyte (neutrophil, PMN) recruitment to the lung followed by loss of elastase from the recruited cells. Dogs were exposed to cigarette smoke with different oxidant content, bronchoalveolar lavage (BAL) was performed, and the cell distribution in the recovered alveolar lining fluid was analyzed. Exposures were 1, 3, or 6 cigarettes on one or multiple days with a maximum dose of 42 cigarettes. The mean percent PMN present in control lavage was 2.01%, while the mean percent PMN recovered in BAL after a dose of 42 1R1 cigarettes was 13.05%. Recoverable PMN, after a single exposure to three 1R1 cigarettes, also increased from 1.7 to 10.4% by 15 h after cessation of smoke exposure. The cell response for multiple (2 and 7) day exposures was similar. The elastase content per BAL neutrophil decreased relative to peripheral blood PMN from the same animals. No free elastolytic activity was found in BAL, but PMN elastase antigen was present. Increased frequency of cigarette smoke exposure delayed the return to homeostatic cell conditions. The increased PMN accumulation observed may result in an increased proteolytic load in the pulmonary interstitium and contribute to the pathogenesis of emphysema.

Do indium 111-labeled polymorphonuclear leukocytes detect neutrophil-prominent, fibrosing lung disease in rats?

The role of polymorphonuclear leukocytes (PMNs) in fibrotic lung disease remains poorly defined, but PMN prominence may predict a poor response to therapy in some patients. The bleomycin injury to rats represents a model of PMN-prominent alveolitis leading to fibrosis. We examined a method of identifying the alveolitis during its PMN-prominent phase with indium 111-labeled homologous PMNs (In-PMNs). When pairs of injured and uninjured rats were compared, greater activity was consistently found persisting in the lung images of the injured rats, both several hours (early) and a day (late) after injection of In-PMNs. Differences could likewise be identified when lung activity was normalized to activity of the injectate, the spleen, and variably the liver, as determined from organ images. These differences in gamma camera images were supported by direct measurement of activity in organs obtained by killing the animals after scanning. When groups of animals were compared, lung/spleen ratios appeared to most consistently differentiate the group of normal animals from those with alveolitis. These methods may provide a noninvasive means of identifying PMN prominence in the lung, which occurs in some fibrotic processes.

Neutrophil chemotaxis in sickle cell anaemia, sickle cell beta zero thalassaemia, and after splenectomy.

Neutrophil chemotaxis was evaluated in 28 patients with sickle cell anaemia, 10 patient with sickle cell beta zero thalassaemia, 25 patients who had undergone splenectomy, and 38 controls. The mean distance migrated by patients' neutrophils was not significantly different from that of neutrophils from controls. Although several immunological variables have been reported to be changed after loss of splenic function, we were unable to show a defect in neutrophil chemotaxis that could account for the increased susceptibility to infection.