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Biomedical subjects

R Scicchitano

Publications and source records attributed to R Scicchitano.

At least 55 records · Page 3Linked to original sources
PubMed1988

Effect of immunologic reactions on rat intestinal epithelium. Correlation of increased permeability to chromium 51-labeled ethylenediaminetetraacetic acid and ovalbumin during acute inflammation and anaphylaxis.

In these studies we compared jejunal permeability to two probes--chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA) (mol wt, 360) and ovalbumin (mol wt, 45,000)--under control conditions, during acute intestinal inflammation, and in response to systemic anaphylaxis. Acute inflammation was produced after infection with Nippostrongylus brasiliensis and rats were studied at day 0 (control), day 4 (early), day 10 (acute), and day 35 (postinfection). At the latter stage, immune rats were also studied during anaphylaxis induced by i.v. N. brasiliensis antigen. In each study, blood and urine were sampled over 5 h after the probes were simultaneously injected into ligated loops in anesthetized rats. In controls, small quantities (less than 0.04% and 0.002% of the administered dose for 51Cr-EDTA and ovalbumin, respectively) appeared in the circulation and plateaued at 1 h. During acute inflammation, the appearance of both probes continued to increase with time. Compared with controls, 5-h values for 51Cr-EDTA and ovalbumin were (a) significantly elevated at day 4 (p less than 0.005), (b) increased approximately 20-fold at day 10 (p less than 0.005 and less than 0.01, respectively), and (c) normal at day 35. Urinary recovery of 51Cr-EDTA followed the same pattern. During anaphylaxis, appearance of the probes in the circulation increased at 1 h to values approximately 10-fold those in controls (p less than 0.001 and less than 0.01, for 51Cr-EDTA and ovalbumin, respectively), and then declined. Urinary recovery of 51Cr-EDTA over 5 h was also significantly increased. We conclude that epithelial barrier function becomes impaired during both acute inflammation and anaphylaxis. In this rat model, gut permeability changes to 51Cr-EDTA reflect gut permeability changes to macromolecular antigens. If similar conditions exist in humans, urinary recovery of 51Cr-EDTA may be useful in monitoring intestinal abnormalities associated with inflammation.

Acute Disease↗
PubMed1987

Distribution of substance P receptors on murine spleen and Peyer's patch T and B cells.

Previous studies have demonstrated that the sensory neuropeptide substance P (SP) can modulate immune responses in vitro. Work from this laboratory has shown that SP enhances immunoglobulin synthesis by murine splenic and Peyer's patch lymphocytes stimulated with concanavalin A. One mechanism underlying these effects is the binding of SP to specific receptors on lymphocytes. We examined the distribution of SP receptors on murine T and B lymphocytes and their subsets by one and two color fluorescence-activated cell sorter analysis. The specificity and nature of binding was examined using radiolabeled SP, and competitive inhibition experiments were performed with cold SP. In cytofluorimetry experiments, both T and B lymphocytes from Peyer's patches and spleen were bound to SP, with those from Peyer's patches having a higher proportion than lymphocytes from the spleen. The majority of T cells from both organs bound SP with binding being evenly distributed between Lyt-1+ and Lyt-2+ cells. Similarly, the majority of B lymphocytes from spleen and Peyer's patches showed SP binding. There were no significant isotype-specific differences within any organ. Studies using 125I-labeled SP showed specific binding to all lymphocyte subpopulations examined. SP receptors were fewer in number on cells isolated from spleen than on cells from Peyer's patches although the dissociation constants were similar for all populations examined. These studies demonstrated that SP receptors are present both on murine T and B lymphocytes from Peyer's patches and spleen. There is no evidence for differential SP receptor expression on distinct lymphocyte subsets in spleen or Peyer's patches.

Animals↗
PubMed1987

Distribution of somatostatin receptors on murine spleen and Peyer's patch T and B lymphocytes.

Recent evidence suggests that the neuropeptide somatostatin (SOM) plays an immunoregulatory role. We demonstrated previously that SOM inhibits concanavalin A-induced cell proliferation and immunoglobulin synthesis by murine Peyer's patch and splenic lymphocytes. Available data suggest that these effects are in part mediated by specific SOM receptors expressed by lymphocytes, but as yet these receptors have not been characterized. Using cytofluorimetry we investigated the distribution and specificity of binding of fluorescent SOM (SOM*) to murine Peyer's patch and splenic T- and B-lymphocyte subpopulations. The specificity of binding was confirmed by radioassay. T and B cells from both organs showed specific binding of SOM*. In Peyer's patches, approximately 50% of all cell populations studied (whole, T- and B-cell-enriched) bound SOM specifically and this was significantly higher than the corresponding splenic lymphocyte populations. Eighty to eighty-four percent of Peyer's patch Thy1.2+, Lyt1+, or L3T4+ cells and 94% of Lyt2+ cells bound SOM. Greater than 80% of B cells from this organ bound SOM (sIgA+ = sIgM+ greater than sIgG+ cells). In spleen, approximately 30% of Thy1.2+, Lyt1+, or L3T4+ cells bound SOM and this was significantly less than the proportion of Lyt2+ cells (53%) which did so. More sIgA+ (89%) than sIgG+ (66%) than sIgM+ (55%) B cells bound SOM*. Although we have previously shown that the effect of SOM on immunoglobulin synthesis was relatively isotype-specific (IgA synthesis was predominantly affected, especially in Peyer's patches) this cannot be explained solely on the basis of preferential expression of SOM receptors by distinct lymphocyte subsets. Instead, it is probably the result of the specific immunological microenvironment in which the lymphocytes reside.

Animals↗
PubMed1987

The differential effect with time of neuropeptides on the proliferative responses of murine Peyer's patch and splenic lymphocytes.

The neuropeptides substance P (SP), somatostatin (SOM), and vasoactive intestinal peptide (VIP) have been shown to modulate lymphocyte DNA, RNA, and immunoglobulin synthesis. We have previously shown that SP enhances while SOM and VIP inhibit proliferation of murine splenic and Peyer's patch lymphocytes when cells were cultured with concanavalin A and neuropeptides for 72 h. Here we show that the effect of neuropeptides, in particular SP, is dependent on the amount of time that lymphocytes are incubated with NP. We found that SOM and VIP always inhibited cell proliferation for incubation times of 2 to 72 h. In contrast when cells were exposed to SP for 24 h or less, there was inhibition of [3H]thymidine uptake by both Peyer's patches and splenic lymphocytes. Significant enhancement in DNA synthesis by lymphocytes from both organs was only seen when cells were incubated with SP for the whole 72 h. We believe that our data may explain some of the conflicting reports regarding the effects of neuropeptides on cell proliferation.

Animals↗
PubMed1987

Neuropeptides and immunity.

Our studies have clearly shown that neuropeptides have a profound effect on immunoglobulin synthesis both in vivo and in vitro. The effects varied according to the neuropeptide added or the tissue from which the lymphocytes were obtained. Substance P caused the most pronounced enhancement of both functions, especially in Peyer's patch cells, where it selectively increased IgA synthesis. Somatostatin was inhibitory, and the effect of vasoactive intestinal peptide varied according to the source of the cells. We have previously shown that neuropeptides also cause mast cell secretion and that only substance P was effective in this regard on intestinal mucosal mast cells. Therefore, we looked for microanatomic relationships between peptidergic nerves and immune effector cells. Mast cells appear to have structural associations with neuropeptides-containing nerves in the intestine. Nerve growth factor, known to promote the growth of sensory afferent and sympathetic nerves, has significant direct effects on mast cells. In vitro, this substance caused enhanced antigen mediated histamine release and, in vivo, extensive mast cell hyperplasia. Also, in humans, we were able to produce increased numbers of mast cell/basophil colonies from peripheral blood in the presence of nerve growth factor.

Animals↗
PubMed1987

Nebulized fenoterol and i.v. aminophylline in acute severe asthma.

We investigated the bronchodilator effect of intravenous aminophylline given after a cumulative dose of nebulized fenoterol of 2.4 mg in 18 patients with acute severe asthma. The mean forced expiratory volume in 1 s (FEV1) +/- SD before treatment was 0.72 +/- 0.22 l. The mean improvement in FEV1 after fenoterol was 0.64 +/- 0.39 l (85% of total improvement) and after aminophylline 0.11 +/- 0.13 l (15% of total improvement). The improvement after aminophylline was statistically significant (p less than 0.01), though quantitatively small. Thirteen patients improved after aminophylline by less than 0.15 l, and in only five was the improvement 0.2-0.4 l. There was no significant change in heart rate and subjective tremor score with treatment, although observed tremor (0 = absent, 4 = maximum) increased from 0.4 +/- 0.6 to 1.3 +/- 1.0 after all treatment. For the majority of patients presenting with acute severe asthma, it is likely that high doses of nebulized beta-2 agonist alone will produce near maximal bronchodilation in the short term.

Acute Disease↗
PubMed1986

Origin of immunoglobulins in respiratory tract secretion and saliva of sheep.

The origin of the immunoglobulins in the upper respiratory tract secretion of sheep was determined by measuring the distribution between plasma and secretion of radiolabelled purified immunoglobulins and albumin. By calculation of the ratio of specific activity for each immunoglobulin between plasma and secretion, it was estimated that about 81% of IgA in secretion was of local origin, whereas IgM, IgG1, IgG2 and albumin were wholly derived from plasma. Estimates of the selectivity of transport of IgA and IgM into both respiratory tract secretion and saliva were obtained by calculation of a selective index relative to IgG1 or IgG2, which do not bind secretory component (SC). This was based on radioactivity ratios after the simultaneous injection of immunoglobulin labelled with different isotopes (IgA or IgM injected with either IgG1 or IgG2). These calculations revealed that both IgA and IgM were selectively transported into respiratory tract secretion and saliva. This provides further support for the proposition that SC-binding immunoglobulins may be transported from serum into secretions at a variety of mucosal sites dependent on SC availability. Since the IgA in serum of sheep is predominantly of gut origin, this provides an opportunity, in addition to relocation of gut-derived plasma cell precursors, by which the gut may contribute to extraintestinal mucosal responses.

Albumins↗
PubMed1985

Quantitation of sheep IgG1, IgG2, IgA, IgM and albumin by radioimmunoassay.

A solid phase radioimmunoassay procedure for the measurement of immunoglobulins (IgG1, IgG2, IgA and IgM) and albumin in sheep body fluids (serum, intestinal lymph, caudal mediastinal lymph, bile, mammary secretions and intestinal secretions) is described. This method was found to be easy to perform, rapid, sensitive and reproducible. Results obtained were consistent with those previously reported using radial immunodiffusion and nephelometric techniques.

Albumins↗
PubMed1985

The effect of lactation on the transport of serum-derived IgA into bile of sheep.

The effect of lactation on the selective transport of IgA from serum into bile and the relationship between volume of milk production and IgA recovery in bile was examined in sheep following intravenous injection of radiolabelled dimeric IgA. Bile: plasma radioactivity ratios for lactating and non-lactating sheep were 6.20 +/- 1.50 and 1.97 +/- 0.35, respectively, and in lactating sheep the milk : plasma ratio was 8.20 +/- 0.81. When biliary flow rates and milk yield were taken into account, 7.3% and 42.0% of the radiolabelled IgA present in plasma at 1 min after injection was recovered in bile and milk, respectively, of low milk yielding ewes, whereas in high milk yielding ewes, recoveries were 4.0% and 66.0%, respectively. The data suggest that during lactation there is an overall increase in transport of IgA into bile, possibly due to the effect of lactogenic hormones on secretory epithelia, but that there may be competition between hepatocytes and mammary epithelial cells for available serum-derived IgA, depending on the secretory activity of the gland.

Animals↗
PubMed1984

Induction and delivery of mucosal immune responses.

The oral cavity is relatively deficient in lymphoid tissue capable of directing the inductive and effector events required for effective mucosal IgA responses to local antigen. Recent evidence regarding a common mucosal immune system has raised new possibilities in immunization of mucosal surfaces. This review describes the role of the intestine in contributing to responses at distant mucosal sites and in particular emphasizes the immune potential of the intestine in determining the success of immunization strategies to control dental caries.

Antigens, Bacterial↗
PubMed1984

Biliary transport of serum IgA in sheep.

The existence of a hepato-biliary pump for IgA has been studied in sheep by measuring appearance of radioactivity in bile after simultaneous i.v. injection of IgG2 and homologous dimeric IgA each labelled with either 125I or 131I. These experiments confirm that in sheep, as in rodents, IgA is the predominant immunoglobulin in bile and is selectively transported into bile from serum relative to IgG2. In addition, there is evidence for local production of IgA in bile presumably by plasma cells within the liver and biliary tree.

Animals↗
PubMed1984

Contribution of intraperitoneal immunization to the local immune response in the respiratory tract of sheep.

The contribution of gut-associated lymphoid tissue (GALT) to the local immune response in the respiratory mucosa of sheep has been investigated. Sheep were primed intraperitoneally (i.p.) with antigen in Freund's complete adjuvant, a procedure known to produce a large IgA-specific antibody-containing cell (ACC) response in intestinal lymph. ACC and their class specificity were then enumerated by double fluorochrome immunofluorescence in respiratory tissues after intratracheal (i.t.) antigen administration. This immunization procedure produced an enhanced IgA-specific ACC response in the upper respiratory tract mucosa compared with either i.t. or i.p. immunization alone and this was not reflected in the regional lymph nodes. Furthermore, chronic drainage of the intestinal efferent lymphatic duct for the duration of the immunization period abrogated the enhanced response in the respiratory mucosa. These data are consistent with the concept of an intermucosal cell circuit with respect to IgA cell precursors, and provide indirect evidence that IgA responses in the respiratory tract can be enhanced by harnessing the immune potential of GALT as a source of IgA precursors by appropriate immunization strategies.

Animals↗
PubMed1984

Immunoglobulin-containing cells and the origin of immunoglobulins in the respiratory tract of sheep.

The amounts of immunoglobulins formed in the respiratory tract of sheep were investigated by comparing the distribution of radiolabelled immunoglobulin between plasma and lymph from the caudal mediastinal lymph node efferent duct which drains 50-70% of lung lymph. In addition, immunoglobulin-containing cells in the lymph node lymph and in the respiratory mucosa were counted by immunofluorescence. Whereas 91.6 +/- 5.92% and 67.73 +/- 10.07% of IgG1 and IgG2 respectively were plasma-derived, only 35.89 +/- 7.09% of IgA was plasma-derived. IgM and albumin were wholly plasma-derived. There was no evidence for selective transport of any immunoglobulins from plasma into lymph. It was estimated that mediastinal lymph node lymph contributed 0.12 g IgA to the circulation daily, the bulk of this being of local origin. There were only few cells expressing IgA in the caudal mediastinal lymph node and its efferent lymph indicating that, unlike gut-associated lymphoid tissue, bronchus-associated lymphoid tissue in sheep is not a major site of IgA cell precursor production. Despite this finding, IgA was the most frequent isotype of Ig-expressing cells in the respiratory mucosa and it is concluded that the locally formed IgA in lymph node lymph originated from mucosal plasma cells. IgM- and IgG-expressing cells were much less numerous than IgA-cells in the mucosa, but were the predominant isotype in the caudal mediastinal lymph node and regional lymph nodes and in mediastinal lymph node efferent lymph. These experiments have established that the respiratory tract of sheep is qualitatively similar to the intestine with respect to immunoglobulin synthesis in that the bulk of IgA is locally derived and a smaller but significant local contribution of IgG1 and IgG2 occurs, but that it is a poor source of IgA cell precursors. This implies that the IgA plasma cell population in the respiratory mucosa probably originates from distant mucosal sites.

Animals↗