Different subsets of circulating angiogenic cells do not predict bronchopulmonary dysplasia or other diseases of prematurity in preterm infants.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease occurring in very and extremely preterm infants undergoing mechanical ventilation. Given the altered lung vascular growth characterizing BPD, circulating angiogenic cells could be useful biomarkers to predict the risk. The objective of the study was to determine whether the percentages of circulating angiogenic cells (CD34+VEGFR-2+, CD34+CD133+VEGFR-2+, and CD45-CD34+CD133+VEGFR-2+ cells), assessed in the peripheral blood at birth by flow cytometry, could be used as markers for the risk of BPD. In one-hundred and forty-two preterm neonates (gestational age less than 32 weeks and/or birth weight less than 1500 g) admitted to our tertiary care Neonatal Intensive Care Unit between 2006 and 2009, we evaluated the percentages of circulating angiogenic cells at birth, at 7 days, and, in a subset of infants (n=40), at 28 days of life. The main outcome was the correlation between cell counts at birth and the subsequent risk of developing BPD. In our study, all the three cell populations failed to predict the development of BPD or other diseases of prematurity. We suggest that these cells cannot be used as biomarkers in preterm infants, and that research is needed to find other early predictors of BPD.

Variation of B-type natriuretic peptide concentrations and intrauterine growth restriction: mother, fetus and newborn.

To evaluate maternal, fetal, neonatal B-type natriuretic peptide (BNP) concentrations related to Intra Uterine Growth Restriction (IUGR). BNP concentrations in 43 IUGR and 35 healthy, Appropriate for Gestational Age (AGA) infants/paired mothers have been compared, from delivery/birth to first month of life. Maternal and IUGR cord BNP concentrations were coupled to fetal ultrasonography. Neonatal echocardiography was performed too. On delivery BNP was higher in all IUGR mothers, suffering or not from gestational hypertension, than in AGA (median 37.14 vs 11.1 pg/ml p=0.002). Maternal BNP was not associated to cord/neonatal BNP or fetal ultrasonographic parameters. Cord BNP was higher in IUGR than AGA newborns (median 23.9 vs 11.4 pg/ml p=0.0007) independently of gestational age, while varied with amniotic fluid (p=0.0044) and umbilical artery flowmetry (p=0.0121). Earlier drop of BNP on day 3 was reported in IUGR neonates (p=0.0001).Ventricular mass change/body weight varied positively in AGA newborns (p<0.001), while declined in IUGR ones (p=0.003). Carrying IUGR fetus is a stress factor resulting in high maternal BNP concentration. Altered fetal ultrasonographic parameters in IUGR newborns lead to higher BNP cord levels. A rapid BNP drop and probable ventricular mass adjustment of IUGR newborns may indicate earlier post-natal cardiovascular adaptation than AGA infants.

Galectin-3 plasma levels and coronary artery disease: a new possible biomarker of acute coronary syndrome.

Inflammation plays a key role in atherosclerosis. Galectin-3 is a macrophage- and endothelium-derived mediator actively involved in the regulation of many aspects of inflammatory cell behaviour. The aim of this study is to quantify plasma Galectin-3 in patients with coronary artery disease (CAD) and different clinical manifestation at the moment of observation in order to verify whether Galectin-3 could be a useful biomarker of atherosclerotic state. We enrolled 125 patients affected by CAD, angiographically documented (70 stable, 55 unstable). They underwent accurate examinations and anamnestic data was collected. The most important traditional risk factors, such as age, hypertension, and body mass index, were reported. Plasma Galectin-3 was quantified using an ELISA kit. Unstable patients (n = 55) had a higher plasma Galectin-3 levels in respect to the stable subjects (27.75 ng/mL (19.27-39.09) vs 6.48 ng/ml (4.88-8.83), p<0.001. A trend in correlation between plasma Galectin-3 levels and number of vessels compromised seems to be present: CAD patients with three-vessel disease had higher levels of Galectin-3 than patients with one-or two-vessel disease (17.39 ng/ml (10.75-29.82) vs 9.18 ng/ml (5.56-23.22), p= 0.058. The significantly higher plasma Galectin-3 levels in patients with unstable angina in respect to the stable angina confirm the involvement of Galectin-3 in promoting macrophage activation and monocyte attraction. Despite the distribution of CAD in patients with acute and chronic coronary disease being similar, we may hypothesize that Galectin-3 could be a useful biomarker of atherosclerotic plaque and in particular of its destabilization.

Preterm newborns are provided with triggering receptor expressed on myeloid cells-1.

Triggering receptor expressed on myeloid cells-1 (TREM-1) and soluble fraction (sTREM-1) are useful markers of infection in adults. Neonates, especially preterm infants, are exposed to high risk of sepsis due to the immature immune system and few data are available regarding TREM-1, mainly focused on the soluble form. We therefore decided to investigate the baseline assessment of TREM-1, membrane and soluble receptors, in preterm newborns without clinical or microbiological evidence of infection, in order to precociously measure the possible changes due to sepsis and compare them to the obtained reference values. Fifty-nine newborns were enrolled in the study. Median and Interquartile range of TREM-1 were: in monocytes 96 percent with 71 Mean Fluorescence Intensity (50-94); in PMNs: 80 percent (68-87); soluble TREM-1: 29.1 pg/ml (14.55-103.93). Monocyte expression and soluble TREM-1 concentrations appeared comparable to healthy adults, while not all PMNs expressed this receptor, possibly due to their immaturity. Birth weight negatively correlated with sTREM-1, while there were no statistical significances with gestational age, maternal age, gender, mode of delivery, patent ductus arteriosus, intrauterine growth restriction, premature rupture of membranes and TREM-1 or sTREM-1. We also reported a statistical relationship between monocyte TREM-1 and surfactant administration and between sTREM-1 and antenatal steroid prophylaxis. Even if untrained, the neonatal immune system of preterm newborns is equipped with TREM-1 system, but further studies are needed to evaluate the functionality in newborns.

Human colostrum T lymphocytes and their effector cytokines actively aid the development of the newborn immune system.

Colostrum contains soluble and cellular components, the latter mainly T lymphocytes. We expanded in vitro colostrum T lymphocytes (CoTL) to evaluate phenotype and capability of cytokine production. We also considered paired cord blood T-lymphocytes (CBTL) representing the newborn "virgin" immune system. CoTL showed memory phenotype while CBTL expressed mainly naïve phenotype. CoTL included a balanced percentage of helper and cytotoxic subsets. We observed higher percentages of IL-2 (p=0.003) and IL-4 (p=0.027) producing cells by helper rather than by cytotoxic T lymphocytes. The greatest percentage of IFN-gamma producing cells was in cytotoxic cells (p=0.0048), while no difference was found for IL-10. Cord blood samples consisted of a statistically significant greater percentage of helper than cytotoxic cells (p<0.001), with a low percentage of cytokine producing cells, confirming the immaturity of the newborns immune system. CBTL percentage of IL-2 producing cells was higher for helper than cytotoxic subset (p<0.001). We observed a greater percentage of IFN-gamma (p=0.001), IL-4 (p=0.003) and IL-10 (p<0.001) producing cells by cytotoxic than helper T lymphocytes. CoTL demonstrated to protect the newborn through the mothers previous immune experience and to supply active cytokines, which can help the postnatal development of both T type 1/T type 2 response.

The -374T/A variant of the rage gene promoter is associated with clinical restenosis after coronary stent placement.

Upregulation of the receptor for advanced glycation end products (RAGE) may play a crucial role in neointimal formation upon vessel injury. The -374T/A variant of the RAGE gene promoter, which has been associated with an altered expression of the cell-surface receptor, could exert a protective effect toward the development of vascular disease. The aim of this study is to determine the impact of this common genetic variant in the occurrence of clinical in-stent restenosis after coronary stent implantation. The -374T/A polymorphism of the RAGE gene promoter was evaluated by PCR-RFLPs in 267 patients with coronary artery disease who underwent coronary stent implantation and a subsequent coronary angiography 6-9 months later for suspected restenosis. In-stent restenosis was assessed by means of quantitative angiography. Carriers of the -374AA genotype showed a significantly reduced risk of developing restenosis after percutaneous transluminal intervention than non-carriers. To determine whether the protective effect of the homozygous AA genotype toward clinical restenosis was independent of potential confounders, we performed multivariable logistic regression analysis. After allowance for clinical and biochemical risk factors and stent length, the AA genotype remained significantly associated with a reduced prevalence of in-stent restenosis. No relation was evident between the RAGE genotype and established cardiovascular risk factors. In conclusion, the -374AA genotype of the RAGE gene promoter could be associated with a reduced risk of in-stent restenosis after coronary stent implantation.

Increased expression of peripheral benzodiazepine receptors on leukocytes in silent myocardial ischemia.

OBJECTIVES: The purpose of this study was to evaluate benzodiazepine receptor expression on leukocytes from patients with symptomatic or silent myocardial ischemia. BACKGROUND: Silent myocardial ischemia is frequently observed in patients with coronary artery disease. Pain can be effectively controlled by various endogenous mechanisms. Benzodiazepines and their receptors play key roles in pain, in interactions with peptide opioids, in inflammation and in the response to stress. METHODS: The study group consisted of 57 patients with reproducible exercise-induced myocardial ischemia. The presence of a constant behavior in the anginal pain perception during both exercise-induced ischemia and daily life was the most important inclusion criterion. Venous blood samples were taken from all patients to evaluate the expression of peripheral benzodiazepine receptors by flow cytometry. The study cohort was classified into two groups: 24 patients who had anginal pain both at home and during the exercise stress test and 33 patients who were asymptomatic during both daily life and exercise-induced ischemia. RESULTS: Flow cytometry analysis showed increased expression of peripheral benzodiazepine receptors on all types of leukocytes in the asymptomatic patients. The difference was statistically significant for lymphocytes (p < 0.005), monocytes (p < 0.001) and granulocytes (p < 0.001). CONCLUSIONS: These data show that expression of peripheral benzodiazepine receptors was higher in patients with silent myocardial ischemia than in symptomatic patients.

Clinical and angiographic correlates of leukocyte activation in unstable angina.

OBJECTIVES: This study sought to evaluate the relation, if any, between clinical and angiographic findings in patients with unstable angina and monocyte and neutrophil CD11b/CD18 receptor density. The expression of HLA-DR molecules on T lymphocytes, an index of activation of these cells, was also investigated. BACKGROUND: Although activation of neutrophils and monocytes has recently been shown in unstable angina, no studies have correlated activation indexes with clinical and angiographic features of patients with this clinical condition. METHODS: Sixty patients underwent diagnostic coronary arteriography and simultaneous blood sampling from the aorta and coronary sinus before injection of contrast medium. Cell surface receptors were detected by direct immunofluorescence evaluated by flow cytometry using monoclonal antibodies tagged with fluorescent markers. RESULTS: In 38 patients with unstable angina, neutrophils and monocytes showed a significantly higher expression of CD11b/CD18 adhesion receptors in coronary sinus than aortic blood (p < 0.0001 and p < 0.001, respectively). When these patients were analyzed according to clinical characteristics or angiographic findings, no difference in CD11b/CD18 receptor expression in coronary sinus blood was found between the various subgroups, except for patients with at least one episode of chest pain at rest within 48 h of coronary arteriography and a higher neutrophil adhesion molecule density than patients who remained asymptomatic (p = 0.04). Lymphocytes in patients with stable and unstable angina showed a similar percent expression of CD2/CD19 and CD3/HLA-DR antigens, with no difference between aortic and coronary sinus blood. CONCLUSION: These results in a larger cohort confirm previous data that neutrophil and monocyte CD11b/CD18 adhesion molecules show a higher expression in the coronary sinus blood of patients with unstable angina. Among clinical and angiographic findings in patients with unstable angina, only the occurrence of chest pain within 48 h of coronary angiography was related to significantly higher values of neutrophil fluorescence intensity, suggesting that the degree of neutrophil activation is related to the proximity of rest angina episodes to blood sampling. Finally, our data do not support the concept of systemic or transcardiac lymphocyte activation in unstable angina.

Increased production of inflammatory cytokines in patients with silent myocardial ischemia.

OBJECTIVES: The aim of the study was to examine the inflammatory cytokines in patients with myocardial ischemia to evaluate whether silent ischemia patients exhibit any particular cytokine pattern. BACKGROUND: Silent myocardial ischemia is frequently observed in patients with coronary artery disease. Various endogenous mechanisms control a patient's perceived intensity of pain. Among them, the inflammatory process and the related cytokine production are known to modulate the threshold for activating the primary afferent nociceptors. METHODS: Seventy-eight patients with reproducible exercise-induced myocardial ischemia were studied: 34 symptomatic patients, with rest and/or stress angina; 44 asymptomatic patients, with no symptoms during daily life activities or during positive exercise stress test. Venous blood samples were taken from all patients to evaluate the expression of CD11b receptors both on neutrophils and monocytes. Frozen plasma samples (at -80 degrees C) were used to quantify the anti-inflammatory (interleukin-4 and -10, transforming growth factor-beta) and the proinflammatory cytokines (tumor necrosis factor-alpha, interferon-gamma, interleukin-1beta and -6). RESULTS: In asymptomatic patients lower CD11b receptor expression and higher concentration of anti-inflammatory cytokines were observed. Proinflammatory cytokine production was similar in the two groups. CONCLUSIONS: The data suggest that an "anti-inflammatory pattern" of cytokine production correlates with silent ischemia and that the immune and inflammatory system activation may be crucial for angina symptoms.

Plasma levels of interleukin 2, 6, 10 and phenotypic characterization of circulating T lymphocytes in ischemic heart disease.

The purpose of this study was to assess lymphocyte receptors expression in patients with ischemic heart diseases, as well as to measure the plasma levels of interleukin (IL) 2, 6 and 10. T Lymphocytes are found in large numbers in human atherosclerotic plaques, indicating that immune and inflammatory mechanisms are important factors in the pathogenesis of atherosclerosis. Recent data have also implicated T lymphocytes in the pathogenetic mechanism of unstable angina and ischemic heart disease. Three groups of patients were studied: 42 with an acute ischemic syndrome (AIS), 36 with stable angina (SA) and 39 healthy controls. To characterize lymphocyte phenotype, flow cytometry was performed in whole-blood samples. IL-2, IL-6 and IL-10 were measured using the ELISA method. Double fluorescence evaluation showed an increase in CD8+/CD11b+ cells (cytotoxic T lymphocytes) and in CD11b+/CD16+CD56+ cells (NK lymphocytes) in the AIS group and in SA group as compared to the control group (P < 0.05 and P < 0.001, respectively). IL-2 was increased in the AIS and SA groups compared to the control group (AIS 4.5 +/- 0.5 pg/ml; SA 6.3 +/- 0.6 pg/ml; controls 2.4 +/- 0.8 pg/ml, P < 0.05), whereas IL-6 was higher in the AIS group than in the other two groups (AIS 10.8 +/- 1.8 pg/ml; SA 1.8 +/- 0.8 pg/ml; controls 1.2 +/- 0.6 pg/ml, P < 0.0001). These data show that patients with ischemic heart disease have an increase in circulating cytotoxic T lymphocytes and in IL-2 plasma levels, irrespective of their clinical presentation, compared to normal control subjects, whereas IL-6 is elevated only in patients with AIS.

Expression of neutrophil and monocyte CD11B/CD18 adhesion molecules at different sites of the coronary tree in unstable angina pectoris.

To assess the site of leukocyte activation in unstable angina, the expression of neutrophil and monocyte CD11B/CD18 adhesion molecules in 26 patients was measured from blood samples taken from the coronary ostium, the coronary sinus, and the coronary artery just distal to the culprit lesion (postobstructive chamber). CD11B/CD18 adhesion molecules detected by direct immunofluorescence evaluated by flow cytometry were significantly higher in the coronary sinus blood than in both the coronary ostium and the postobstructive chamber blood, suggesting that leukocyte activation takes place at the microcirculatory interface with the injured myocardium, probably as the result of short but repeated episodes of myocardial ischemia.

The role of integrins in granulocyte dysfunction in myelodysplastic syndrome.

The aim of the present study was to evaluate the function of granulocytes in 20 patients affected by myelodysplastic syndrome (MDS) and correlate this with the expression of surface membrane integrins. The granulocytes showed a deficit in chemotaxis (34 +/- 12 vs 84 +/- 10, p < 0.01) in superoxide release (12 +/- 7 vs 30 +/- 10, p < 0.01) and in aggregation 12 +/- 6 vs 36 +/- 9, p < 0.01 using fMLP as stimulus. We also demonstrated with cytofluorimetric and alkaline phosphatase immunoenzymatic analysis (APAAP), decreased expression of CD11b/CD18 receptor detected by OKM1 (p < 0.001) and CD18 detected by MoAb IOT-18 (p < 0.001). PMNs CD11b/CD18 up-regulation and APAAP image analysis studies showed a lower level of expression of CD11b/CD18 in granulocytes from MDS patients compared to controls (p < 0.001). We concluded that granulocyte dysfunction in MDS may be correlated with modification of leukocyte integrins.

Granulocyte dysplasia and dysfunction, and CD11/CD18 defects in myelodysplastic syndromes.

In myelodysplastic syndromes (MDS), dysplastic changes in neutrophils are a common feature reflecting the total degree of bone marrow dysplasia. Furthermore, granulocyte function is abnormal, so that a high risk of life-threatening infections has been documented. In this review we shall focus on the defects of both granulocytes and their CD11b/CD18 glycoprotein complex, which regulate granulocyte adherence, locomotion, diapedesis and migration into inflammatory sites, in patients suffering from primary MDS. The defective surface membrane glycoprotein expression of myelodysplastic phagocytes is not only a useful diagnostic tool, but also a powerful prognostic one, since MDS patients with such defects present both an increased susceptibility to infections and a decreased survival. Moreover, the administration of colony-stimulating factors is known to be able to elicit long-lasting improvement in neutrophil count, CD11b/CD18 expression and function, marrow myeloid maturation, and possibly to decrease bacterial infections in MDS patients.

In vitro effects of GM-CSF on mature peripheral blood neutrophils.

GM-CSF can play a crucial role in regulating the neutrophil-mediated inflammatory response. This growth factor is a proliferative stimulus for bone marrow neutrophil stem cell precursors and has at least 3 important roles in regulating neutrophil-mediated immunity: a) a direct effect on the proliferation and development of neutrophil progenitors; b) synergistic activity with other haemopoietic growth factors; c) stimulation of the functional activity of mature neutrophils. The production of GM-CSF may be triggered directly by exogenous factors such as antigens and endotoxins, or indirectly through the release of cytokines by a variety of cells including lymphocytes, activated macrophages and endothelial cells exposed to products of mononuclear phagocytes. Such production of GM-CSF may serve to quickly release mature neutrophils from the bone marrow in response to infections. Moreover, enhancement of the function of mature neutrophils may also augment their ability to migrate to infective sites and then phagocytose and kill pathogens. Increased expression of CD11b/CD18 may play a fundamental part in this mechanism because this receptor is essential for the adhesion of neutrophils to the endothelium. Both phagocytosis and oxidative burst activity increase as a result of the action of GM-CSF and the increased expression of complement- and Fc-receptors can augment opsono-phagocytosis. A further level of neutrophil up-regulation occurs by increasing the functional life span of neutrophils by GM-CSF. Thus, by delaying neutrophil apoptosis, GM-CSF greatly extends the time over which neutrophils may function at inflammatory sites. GM-CSF can thus exert a variety of important regulatory controls of neutrophil function during bacterial infections. Both the number and the functional status of neutrophils is highly regulated by GM-CSF. It is also possible that GM-CSF produced within localised sites of acute inflammation or infection may attract, trap and then activate neutrophils within this site.

[The role of the granulocytes in ischemic cardiopathy]. / Ruolo dei granulociti nella cardiopatia ischemica.

Recent studies suggest that granulocytes (PMNs) play a role in the pathogenesis of acute and chronic myocardial ischemia and extension of myocardial injury. Granulocytes can release a variety of mediators tissue injury and synergize with these different mediators, cytokines and other cells resulting in amplification of neutrophil stimulation and rising to additional products with enhanced endothelial injury. Free radicals released by PMNs during ischemia or reperfusion produce deleterious effects on cell membranes, endothelial cells and myocardium. Experience in humans shows the modification of PMNs function in angina and during myocardial ischemia: upon reperfusion PMNs accumulate and produce an inflammatory response leading to endothelial injury. Rabbit derived antiserum dependent-reduction of circulating PMNs in the dog or using monoclonal antibody anti-CD11b/CD18 of PMNs resulted in smaller myocardial infarction. Another aspect of PMNs function is related to leukotriene C4 release; the vasoconstrictor effect of this leukotriene on coronary arteries is synergistic with that induced by platelet-released thromboxane A2, and the decrease in coronary flow produced by the combination of both substances is greater than the sum of changes caused by the two eicosanoids separately administered. The potential role of leukocytes, oxygen radicals, leukotrienes and granulocyte enzymes in the pathophysiology of myocardial injury due to regional ischemia and reperfusion is an area of intense investigation. This overview will not attempt to be exhaustive. Experimental and clinical studies to elucidate these events should not only provide insight into acute and chronic pathologic tissue damage, but may also lead to the identification of important new targets of pharmacologic intervention.

[Job syndrome (hyper-IgE) and hypo-IgA. A rare association of immunodeficiencies]. / Sindrome di Giobbe (Iper-IgE) ed ipo-IgA. Rara associazione di immunodeficienze.

Job' syndrome and IgA immunodeficiency are a rare dysfunction of the immune system. In this work, we reported a case of a young woman who had recurrent episodes of bacterial infections in the urinary tract and genital, generalized erythematous eczematous patches and stomatitis of oral mucosa and fever. During the hospitalization, laboratory data showed high immunoglobulin IgE and low IgA levels. The T-lymphocyte presented a reduction of CD8+ cells. Tests of granulocyte function have showed a global deficit in the in vitro and in vivo chemotaxis. The correlation between these two clinic conditions is not completely clarified but it is possible to hypothesize that CD8+ lymphocytes produce an inhibition factor of chemotaxis. Job' syndrome is characterized by a selective reduction of CD8+ cells subpopulation which have an immunoregulatory function on the production of IgE by plasmacells. In the ipoIgA, an intrinsic inability of B-IgA cells to proliferate and to differentiate produce a defect in the IgA production. In these two clinic disorders there is an effective dysfunction of immune system. It is possible to hypothesize that an effective defect of CD8+ cells and an immaturity of B-cells may coexist in our patient. That justifies an abnormal production of Ig and a defect in granulocyte chemotaxis.

Solitary extramedullary plasmacytoma.

A rare case of abdominal plasmacytoma is described. A computed guided biopsy of abdominal mass permitted an accurate diagnosis. Blood findings revealed an increased gamma-globulin level and serum immunoelectrophoresis revealed high IgG-kappa spike. Bone marrow biopsy resulted negative for neoplastic infiltration. Plasmacytoma is a malignant proliferation of differentiated B lymphocytes which produce immunoglobulin. In our case, microscopically, biopsy of abdominal mass revealed the presence of plasmablasts with bizarre multiforme nuclei, spindled contours and positive immunoenzymatic reaction for CD38, suggestive for plasma cell proliferation.

[beta-Interferon therapy of chronic hepatitis HCV+, 1b genotype]. / La terapia con beta-interferone dell'epatite cronica HCV+, genotipo 1b.

Various papers reported that chronic viral hepatitis is the principal cause of chronic liver disease, as cirrhosis and hepatocarcinoma. Interferon is the only agent known to have a beneficial effect in chronic hepatitis. The response rate has been less than 10 percent in patients with genotype 1b, but in patients with genotype 2 or 3 it has been greater than 40 percent. Aim of our investigation was to study 10 patients suffering from chronic viral hepatitis HCV related, genotype 1b, non responder to interferon-alpha therapy. In these patients we administered beta-interferon at the dose of 6 million units, 3 times a week, for 3 months. A significant reduction of aminotransferase level was reported after 3 months of the start of the therapy. An higher level of beta-interferon plasma rate was found in 3 non responder patients. The interaction of beta-interferon with the immune system was demonstrated with an increase of CD8+ lymphocytes that correlated with decrease of HCVRNA. The treatment with beta-interferon have a beneficial effect in patients with chronic hepatitis HCV related, genotype 1b, no responder to interferon-alpha therapy.

[Opioid receptors and phagocyte defects in drug addicts]. / Recettori oppioidi e difetti dei fagociti in pazienti tossicodipendenti.

In order to better elucidate the immunological effect of opioid abuse in the absence of HIV infection as a confounding factor, granulocyte function was investigated in 3 groups of HIV negative subjects including 20 active parenteral heroin abusers (E), 20 long-treatment methadone-maintained former opiate abusers (M) and 20 healthy controls. Chemotaxis to fMLP, casein and activated plasma were markedly and similarly reduced (approximately 50%) in both E and M groups, as true for superoxide production after fMLP and PMA stimulation, 47% decrease of C values. PMNs of E and M subjects also exhibited a very marked and similar reduction in the expression of CD11b/CD18 integrin receptors after fMLP treatment with values that were lower than 10% of those in controls as observed by flow cytometry. In parallel, PMNs of E and M individuals presented an approximately four fold increase in opioid receptors number compared to controls, a significant inverse correlation existing between the increase in opiate receptors and defective chemotaxis. The possible mechanism retaining the observed changes in PMNs of E and M individuals are discussed.

[Correlations between membrane integrins and granulocyte defects in myelodysplastic syndromes]. / Correlazione tra integrine di membrana e difetti dei granulociti nelle sindromi mielodisplastiche.

The aim of the present study was to evaluate some functions of neutrophil granulocytes (PMNs), such as aggregation, superoxide production, chemotaxis and adhesion molecules involved in these processes, in 22 patients suffering from Myelodysplastic Syndrome (MDS), to clarify if granulocytes alterations described in this syndrome is really correlated with the expression of surface membrane integrins. Several patients suffering from MDS present granulocytopenia and/or absolute monocytoses; neutrophil granulocytes can have typical nuclear and cytoplasmatic alterations. These granulocytic anomalies are valuable in about 90% of patients suffering from MDS. The granulocytes showed a significant deficit in chemotaxis stimulated by serum activated with E. Coli, casein and formyl-methionyl-leucylphenylalanine (fMLP) (p < 0.01) and in superoxide production stimulated by phorbol-myristate-acetate (PMA). We also studied the role of membrane integrin CD11/CD18 using specific monoclonal antibodies (MoAb). The cytofluorimetric analysis demonstrated a significant inhibition in expression of CD11b/CD18 receptors in patients suffering from MDS (p < 0.001), while the expression of CD11a/CD18 and CD11c/CD18 receptors was normal. In conclusion we found specific alterations in PMNs functions in MDS and a correlation of these anomalies with membrane integrins of PMNs is therefore possible.