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Biomedical subjects

B S Polla

Publications and source records attributed to B S Polla.

At least 109 records · Page 6Linked to original sources
PubMed1991

The heat shock response in human phagocytes.

During the last 10 years the intriguing field of the heat-shock response and stress proteins has switched from a particular case to a phenomenon of general interest. Discovered in Drosophila, these proteins were observed in every living organism with a surprisingly high sequence homology. In addition, these proteins are not only inducible by stress or pathophysiological situations but are also expressed in unstressed cells. These are arguments for crucial roles of heat-shock proteins. Here we discuss some aspects of the heat shock/stress response that we observed in phagocytic cells after phagocytosis with regard to their physiologic functions such as oxygen-free radical generation, antigen processing and presentation.

Antigen-Presenting Cells↗
PubMed1991

Heat shock proteins in host-parasite interactions.

For most living organisms, heat shock represents an unusual stress situation, but for parasites that are transmitted between invertebrate vectors and mammalian hosts it is a frequent physiological occurrence. Because of the extraordinary conservation of heat shock proteins (HSPs) and their potential immunogenicity, much attention has recently focused on the role of HSPs in infection and immunity. In parasites, HSPs appear to play specific functions in differentiation, in protection from the host cell's killing mechanisms, including oxygen free radicals, and even in virulence. In this article, Barbara Polla uses the example of malaria to illustrate the possible role of HSPs in host-parasite relationships.

Animals↗
PubMed1991

Superoxide production by peripheral blood monocytes during sustained endotoxaemia in sheep.

1. We have studied the time course of the numbers of arterial monocytes and their superoxide anion (O2-) production in a chronically instrumented sheep model of subacute endotoxaemia induced by a continuous intravenous infusion of Escherichia coli lipopolysaccharide (20 ng min-1 kg-1). 2. Four out of 11 animals died from irreversible respiratory and cardiovascular failure within 21 h of the start of lipopolysaccharide administration ('non-survivors'), whereas in the seven surviving sheep ('survivors') there was a persistence of decreased systemic vascular resistance, systemic hypotension, pulmonary hypertension, anorexia and lethargy. 3. O2- generation by isolated monocytes was measured by the O2- dismutase-inhibitable reduction of ferricytochrome c after stimulation with phorbol myristate acetate (100 ng/ml) or opsonized zymosan (3 mg/ml). Basal mean value of phorbol myristate acetate-stimulated O2- production was significantly (P = 0.008) higher for non-survivors (31.3 +/- 8.8 nmol 30 min-1 10(-6) cells; n = 4) than for survivors (6.2 +/- 2.3 nmol 30 min-1 10(-6) cells; n = 7). 4. For both survivors and non-survivors, monocyte counts and phorbol myristate acetate-stimulated O2- production increased over time to reach in survivors a plateau after 2 days of continuous lipopolysaccharide infusion. Similar results were obtained when monocytes were stimulated for O2- production with opsonized zymosan. 5. These results suggest that (1) increased O2- production by monocytes and monocytosis appear with a precise, delayed time course during the development of subacute endotoxaemia in sheep; and (2) a high stimulated O2- production by monocytes before lipopolysaccharide administration may represent a predictive factor for the subsequent respiratory failure and outcome of endotoxaemia.

Animals↗
PubMed1991

Improvement of symptoms of non-allergic chronic rhinitis by local treatment with capsaicin.

Sixteen adult patients suffering from severe chronic non-allergic rhinitis with nasal vasoconstrictor abuse for more than a year, received, under local anaesthesia, an intranasal spray of capsaicin (3.3 x 10(-3) mol), the pungent agent in hot pepper, once weekly for 5 weeks. The subjective intensity of their nasal obstruction, rhinorrhoea and sneezing frequency were evaluated throughout the study and the vascular effects of capsaicin on the nasal mucosa were recorded by anterior rhinomanometry and laser Doppler flowmetry. Calcitonin gene-related peptide (CGRP) is a vasodilator agent present in sensory nerves and may play a major role in the vascular component of neurogenic inflammation. Therefore, the nasal mucosa content of CGRP-like immunoreactivity (CGRP-LI) was determined by radioimmunoassay in biopsies obtained before and after the capsaicin treatment. Intra-nasal capsaicin application evoked a larger vascular response in patients with rhinitis than in controls (P less than 0.05). Both nasal vascular responses and subjective discomfort following capsaicin were markedly reduced after the fifth application (P less than 0.01). In parallel, a 50% reduction of the CGRP-LI content in the nasal biopsies was observed. All symptoms were significantly improved throughout a 6 month follow-up period. No significant side-effects occurred and weaning from nasal vasoconstrictor agents was possible. Both the subjective symptom score and objective measurements of vascular reactivity suggest that repeated intra-nasal capsaicin application could be beneficial for patients with chronic rhinitis, possibly by reducing hyperreactive nasal reflexes.

Administration, Intranasal↗
PubMed1991

Phagocytosis and heat shock response in human monocytes-macrophages.

The heat shock response represents a general physiological cellular reprogramming of gene expression secondary to exposure to multiple different stresses such as heat or oxygen free radicals. It is assumed that this response is turned on in order to protect cells, or to permit better recovery, from the detrimental effects of such stresses. During erythrophagocytosis, heat shock proteins and heme oxygenase synthesis are induced in human monocytes-macrophages. Whereas induction of heme oxygenase appears to be related to the hemoglobin-released iron, the factor(s) responsible for heat shock protein induction remain elusive. The respective roles of phagocytosis itself, oxygen free radicals, calcium, cytoskeletal alterations and oncogene expression are discussed.

Calcium↗
PubMed1991

Heat shock proteins: an autoprotective mechanism for inflammatory cells?

Heat shock/stress proteins are synthesized in all cell types under a variety of stressful conditions. Stress associated with ongoing inflammation relates, at least in part, to toxic products locally generated by cells accumulating in the inflamed tissue and organ. These products include oxygen free radicals, cytokines, proteases, chemotactic factors and, in the particular case of the eosinophil, toxic basic proteins. The heat shock response in inflammatory cells appears to be specifically regulated by their own proinflammatory products (oxygen free radicals, cytokines) generated during physiological functions such as phagocytosis, during differentiation, or in certain pathological states such as inflammatory lung diseases. We suggest that in human monocytes-macrophages heat shock proteins belong to the autoprotective equipment against oxidative stress.

Animals↗
PubMed1991

[Cheese-washer's disease. A current stable form of extrinsic allergic alveolitis in a rural setting].

Inhalation of organic particles (bacteria, fungi or animal proteins) by sensitized subjects is known to induce extrinsic allergic alveolitis (EAA). The most frequent type of EAA and the best known in rural environment is farmer's lung disease. Nevertheless a rarer form is also to be considered in rural environment: cheesewasher's disease. Here we report 4 cases of cheesewasher's disease, who all presented with relevant aspects of the disease: diversity of antigens involved, prophylaxis problems, severity of the disease, rapidity of onset, reversibility and importance of history in the diagnosis. Penicillium casei usually is the responsible antigen, and precipitating antibodies against these moulds, but against other moulds such as Aspergillus, Circinomucor circilloïdes, Fusarium as well, can be detected in the patient's serum. Thus, in a rural environment, a respiratory symptomatology suggestive of EAA should lead to thorough search for antigens and cheesewasher's disease should be considered. Among the many other diagnostic tests, precipitin determinations are cheap and non invasive and can be very useful in the diagnostic approach.

Adult↗
PubMed1990

Protection from cellular oxidative injury and calcium intrusion by N-(2-mercaptoethyl)-1,3-propanediamine, WR 1065.

The radioprotective agent WR 2721 has been shown to prevent deterioration of renal function in a rodent model of chronic renal failure, and it has been suggested that WR 2721 may exert these protective effects by scavenging free radicals. To test this hypothesis, we investigated the effects of WR 2721 and its dephosphorylated, active metabolite, WR 1065, in an in vitro model of oxidative injury. By using the classical assay for superoxide production (reduction of ferricytochrome c), we first demonstrated that WR 1065 may act as a reducing agent. To establish the biological relevance of this reducing ability, U937 cells (a human premonocytic line) were incubated with or without WR 1065 or 2721, then exposed to increasing concentrations of H2O2. Cell viability was measured by Trypan blue exclusion and [3H]-thymidine incorporation into DNA, and cytosolic free calcium determined by fura-2 fluorescence. WR 1065 protected U937 cells from H2O2-induced cell death in a dose-dependent manner, and more efficiently than WR 2721. WR 1065 also prevented the rise in cytosolic free calcium induced in these cells by H2O2. These in vitro molecular and cellular events may account, at least in part, for the in vivo protective effects of WR 2721.

Amifostine↗
PubMed1990

123I-MIBG pulmonary removal: a biochemical marker of minimal lung endothelial cell lesions.

Circulating biogenic amines, such as serotonin or norepinephrine, are cleared by the lung and can be considered as indicators of pulmonary endothelial integrity. An iodinated norepinephrine analogue, metaiodobenzylguanidine (MIBG), is extracted in the lung by an active, saturable transport system. In order to investigate the use of MIBG lung extraction to detect minimal lung endothelial cell lesions, an experimental model of initial pulmonary vascular lesions was developed in rats using repeated daily intraperitoneal injection of bleomycin (BLM: 2 U/100 g body weight) over a 5-day period. At this time, a significant decrease of serum angiotensin-converting enzyme activity, an index of endothelial cell metabolism, was observed (214 +/- 11 U/ml in controls as compared with 182 +/- 11 U/ml in BLM-treated rats, P less than 0.05); electron microscopy showed the presence of typical but minimal endothelial cell lesions (blebbing). MIBG extraction (%EMIBG) was measured using the isolated perfused lung model after a 10-min steady-state period and 2 min of perfusion with 123I-MIBG (0.1 microCi/ml) and 125I-labelled human serum albumin (HSA) (0.2 microCi/ml). Intraperitoneal administration of BLM to rats for 5 days resulted in a significant decrease in pulmonary extraction of MIBG. %EMIBG declined from a control value of 24.7% +/- 1.1% in controls to 19.3 +/- 1.6% in BLM-treated rats (n = 27, P less than 0.05; -21.2%). HSA lung extraction, used as an estimate of nonspecific residual lung activity, was not different in the lungs of BLM-treated rats as compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Iodobenzylguanidine↗
PubMed1990

1,25-Dihydroxyvitamin D3 increases the toxicity of hydrogen peroxide: the role of calcium and heat shock.

1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] increases synthesis of heat shock proteins in monocytes and U937 cells and protects these cells from thermal injury. We therefore examined whether 1,25-(OH)2D3 would also modulate the susceptibility to H2O2-induced oxidative stress. Prior incubation for 24 h with 1,25-(OH)2D3 (25 pM or higher) produced unexpected increased H2O2 toxicity. Since cellular Ca2+ may be a mediator of cell injury, we investigated the effects of altering extracellular Ca2+ ([Ca2+]e) on 1,25-(OH)2D3-enhanced H2O2 toxicity, as well as the effects of 1,25-(OH)2D3 and H2O2 on cytosolic-free Ca2+ concentration ([Ca2+]f). Basal [Ca2+]f in medium containing 1.5 mM Ca2+ as determined by fura-2 fluorescence was higher in 1,25-(OH)2D3-pretreated cells than control cells (137 versus 112 nM, p less than 0.005). H2O2 induced a rapid increase in [Ca2+]f (to greater than 300 nM) in both 1,25-(OH)2D3-treated and control cells, which was prevented by a reduction in [Ca2+]e to less than basal [Ca2+]f. The 1,25-(OH)2D3-induced increase in H2O2 toxicity was also prevented by preincubation with 1,25-(OH)2D3 in Ca2(+)-free medium or by exposing the cells to H2O2 in the presence of EGTA. Preexposure of cells to 45 degrees C for 20 min, 4 h earlier, partially prevented the toxic effects of H2O2 particularly in 1,25-(OH)2D3-treated cells, even in the presence of physiological levels of [Ca2+]e. Thus, 1,25-(OH)2D3 potentiates H2O2-induced injury probably by increasing cellular Ca2+ stores. The protective effects of heat shock are probably exerted at a site distal to the toxic effects of Ca2+. The 1,25-(OH)2D3-induced amplification of the heat shock response likely represents a mechanism for counteracting the Ca2(+)-associated enhanced susceptibility of oxidative injury due to 1,25-(OH)2D3.

Calcitriol↗
PubMed1990

Erythrophagocytosis induces heat shock protein synthesis by human monocytes-macrophages.

Exposure of cells to elevated temperatures and other environmental stresses results in the expression of specific genes encoding the so-called heat shock proteins (HSPs). Since exogenous H2O2 induces in human monocytes the synthesis of HSPs, and previous induction of HSPs protects these cells from oxidative injury, we investigated whether HSP synthesis was also induced during generation of reactive oxygen species by the phagocyte itself during phagocytosis. As a model system, we analyzed the effects of erythrophagocytosis on protein synthesis by the human premonocytic line U937, in which phagocytosis is induced during differentiation with 1,25-dihydroxyvitamin D3. Exposure to whole erythrocytes, but not to erythrocyte ghosts, induced in the phagocytic cells only the synthesis of the 70- and 83- to 90-kDa HSPs and a 32-kDa oxidation-related stress protein identical by partial peptide mapping to heme oxygenase. The radioprotective aminothiol N-(2'-mercaptoethyl)-1,3-propanediamine (WR-1065), which can substitute for glutathione as hydrogen donor, prevented this induction. These results suggest that oxygen free radicals generated in the presence of hemoglobin-derived iron and consecutive glutathione depletion are involved in induction of stress protein synthesis during erythrophagocytosis. HSPs synthesized during phagocytosis may play a role in the phagocyte's defense mechanisms and in protective immunity.

Animals↗