POLYMORPHONUCLEAR PHAGOCYTOSIS AND KILLING IN WORKERS EXPOSED TO INORGANIC MERCURY

The ability of neutrophils to phagocytose- and kill Candida species as well as the splenic phagocytic function were investigated in workers from a mercury-producing plant. In the neutrophil phagocytosis study, two species of Candida were used since in individuals with myeloperoxidase deficiency neutrophils are unable to kill Candida albicans, while Candida pseudotropicalis can be effectively lysed. Phagocytosis of both antigens and splenic phagocytic function were normal in all the workers studied. However, following ingestion of the organisms there was considerable reduction in the ability of neutrophils from exposed workers to kill both species of Candida, and this was not explained by a mild impairment of phagocytosis. After improvement in the hygiene conditions in the factory, a new evaluation was performed, 6 months later, in the same workers and urinary mercury concentrations were determined monthly in each worker. Despite a significant reduction in urinary mercury concentrations, a greater impairment in the ability of neutrophils to kill C. albicans was observed. The killing of C. pseudotropicalis presented no further impairment when compared to the previous evaluation. These results suggest that impairment of the lytic activity of neutrophils from workers with urinary mercury concentrations within the safe level for exposed population is due, at least in part, to some interference with myeloperoxidase activity. In addition, the mercury-NADPH complex, once formed, could limit the utilization of reduced pyridine nucleotides by NADPH-dependent enzymes such as NADPH oxidase, thereby inhibiting the PMN respiratory burst.16121011101

Early circulating erythroid progenitor cells and expression of erythropoietin receptors in sickle cell disease

The ability of circulating progenitor cells from 22 patients with sickle cell disease (SCD) to develop erythroid colonies was studied in vitro in the presence or absence of growth factors (5637-CM and erythropoietin). In both conditions, SCD patients presented significantly higher numbers of circulating burst-forming unit-erythroid (BFU-E/5x10(5)MNC) when compared to control subjects. The study of the expression of erythropoietin receptors revealed an increased level in SCD patients. Moreover, there was a correlation between both stimulated and autocrine (without stimulus) BFU-E and the expression of erythropoietin receptors. These results are of particular interest since they indicate that the phenomenon of spontaneous BFU-E-derived colonies observed in SCD patients may be due to an increased expression of erythropoietin receptors.60422623

Immunoglobulin levels in workers exposed to hexachlorobenzene

The serum immunoglobulin (IgG, IgM and IgA) concentrations of 52 chlorinated-exposed workers were examined and compared with those of non-exposed, age-and sex-matched individuals. At the time of testing, the exposed population had mean hexachlorobenzene (HCB) blood levels of 3.84 mu g/dl with a range of 0.1 to 16 mu g/dl. Increased IgG and IgM levels were found in the HCB-exposed workers (P<0.05 and P<0.01, respectively). Hepatic function was evaluated by serum aspartate (AST) and alanine aminotransferase (ALT) activities, as well as by bilirubin levels. IgM concentrations were positively correlated with three of the studied parameters, namely, length of exposure (r=0.367) and the activities of both AST (r=0.367) and ALT (r=0.507).17317217

IMMUNOGLOBULIN LEVELS IN WORKERS EXPOSED TO INORGANIC MERCURY

The serum immunoglobulin (IgG, IgM and IgA) concentrations of 44 mercury-exposed workers were examined and compared with those of non-exposed, age- and sex-matched individuals. At the time of testing, the exposed population had a mean (+/- S.D.) mercury urinary concentration of 24.7 +/- 19.1 and in 40 of them urinary mercury levels were below the currently accepted limit of 50 mu g/g creatinine. Increased IgG, IgA and IgM levels were found in the mercury-exposed individuals and in 16, a second evaluation was performed six months later. During the intervening six months, the level of hygiene was improved throughout the plant, and urinary mercury concentrations were determined monthly in each worker. Despite a significant reduction in mercury urinary concentrations, serum immunoglobulin levels did not return to the normal range. There was no correlation between the length or level of exposure and the immunoglobulin levels. Liver protein synthesis, as studied by factor V, prothrombin time, prealbumin and transaminase activity, was normal and liver injury, as evaluated by serum aspartate and alanine aminotransferase activities (AST and ALT, respectively), was not observed. No haemotological abnormalities were noted. These results indicate that ''safe'' levels of mercury exposure may lead to humoral immunological stimulation.742727

Hydroxyurea promotes the reduction of spontaneous BFU-e to normal levels in SS and S/beta thalassemic patients

We have studied the effects of hydroxyurea on growth and differentiation of early erythroid progenitor cells (BFU-e) from peripheral blood of sickle cell disease patients (five SS and two Hb S/beta -thalassemia) in the presence or absence of exogenous stimulating factors. When the mononuclear cells from the sickle cell disease patients were cultured at diagnosis (before hydroxyurea treatment), there was an increased number of BFU-e in relation to controls (p < 0.05, Wilcoxon test) when cells were grown in the presence or absence of 5637 conditioned medium and erythropoietin. Colonies that developed in the absence of added growth factors were considered "spontaneous". A significant difference was observed after hydroxyurea treatment in the number of BFU-e obtained in the presence and absence of stimulus, with a higher reduction in the spontaneous BFU-e number. As expected, there was an increased Hb F level in these patients when compared with their pretreatment levels. There was no correlation between spontaneous BFU-e and hemoglobin levels in all patients studied.2511

Defective neutrophil function in workers occupationally exposed to hexachlorobenzene

In this work rye have studied the respiratory burst and chemotaxis of polymorphonuclear leukocytes from 51 workers exposed to chlorinated compounds, which were compared with those of non-exposed, age- and sex-matched invididuals. These two neutrophil functions were significantly reduced as compared to controls. No correlation was observed between the length of exposures, hexachlorobenzene (HCB) blood concentrations and neutrophil chemotaxis or the extent of nitroblue tetrazolium reduction.16632232

IMMUNOGLOBULIN LEVELS AND CELLULAR IMMUNE FUNCTION IN LEAD-EXPOSED WORKERS

The immunological status of lead acid battery workers with blood lead levels and urinary delta-aminolevulinic acid (ALA-U) concentrations ranging from safe to toxic levels has been examined and compared with those of non-exposed, age and sex matched controls. No differences in the serum concentrations of IgG, IgA and IgM between the populations were observed and there existed no correlation between blood lead level or ALA-U concentrations and serum immunoglobulin levels. In addition assessment was made of the capacity of peripheral blood mononuclear cells to respond to the mitogen phytohaemagglutinin (PHA), a correlate of T cell function. As before, there was no difference between exposed and control populations and no correlation between reactivity and blood lead concentration. Our data Suggest that chronic exposure to lead fail to compromise lymphocyte function in man.16111512

ENGULFMENT AND KILLING CAPABILITIES OF NEUTROPHILS AND PHAGOCYTIC SPLENIC FUNCTION IN PERSONS OCCUPATIONALLY EXPOSED TO LEAD

Phagocytosis and intracellular killing of Candida albicans and Candida pseudotropicalis by neutrophils as well as phagocytic splenic function from lead-exposed workers were studied. Two species of Candida were used since in individuals with myeloperoxidase deficiency neutrophils are unable to kill C. albicans, whereas C. pseudotropicalis can be effectively lysed. Phagocytosis with both antigens and phagocytic splenic function were normal in all the workers studied. However, lytic activity towards C. albicans, but not C. pseudotropicalis was impaired. This defect was observed in lead-exposed workers with blood lead levels and urinary delta-aminolevulinic acid (ALA-U) concentrations in the ''safe'' (below 60 ug/dl and 6 mg/l, respectively) and toxic ranges. An impaired ability to kill C. albicans suggests that lead exposure may lead to a myeloperoxidase deficiency. With the exception of blood lead levels and ALA-U concentrations, there was no correlation between any of the other parameters examined.16323924

Assessment of the Myogenic Stem Cell Compartment Following Transplantation of Pax3/Pax7-Induced Embryonic Stem Cell-Derived Progenitors

An effective long-term cell therapy for skeletal muscle regeneration requires donor contribution to both muscle fibers and the muscle stem cell pool. Although satellite cells have these abilities, their therapeutic potential so far has been limited due to their scarcity in adult muscle. Myogenic progenitors obtained from Pax3-engineered mouse embryonic stem (ES) cells have the ability to generate myofibers and to improve the contractility of transplanted muscles in vivo, however, whether these cells contribute to the muscle stem cell pool and are able to self-renew in vivo are still unknown. Here, we addressed this question by investigating the ability of Pax3, which plays a critical role in embryonic muscle formation, and Pax7, which is important for maintenance of the muscle satellite cell pool, to promote the derivation of self-renewing functional myogenic progenitors from ES cells. We show that Pax7, like Pax3, can drive the expansion of an ES-derived myogenic progenitor with significant muscle regenerative potential. We further demonstrate that a fraction of transplanted cells remains mononuclear, and displays key features of skeletal muscle stem cells, including satellite cell localization, response to reinjury, and contribution to muscle regeneration in secondary transplantation assays. The ability to engraft, self-renew, and respond to injury provide foundation for the future therapeutic application of ES-derived myogenic progenitors in muscle disorders. STEM CELLS 2011;29:777-790295777790Dr. Bob and Jean Smith FoundationNIAMS [AR055299]NIA at the National Institutes of Health [AG034370]NIAMS [AR055299]NIA at the National Institutes of Health [AG034370