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Biomedical subjects

J B Hay

Publications and source records attributed to J B Hay.

At least 73 records · Page 4Linked to original sources
PubMed1982

Pathways to inflammation induced by immune complexes: development of the Arthus reaction.

The changes associated with inflammation induced by immune complexes (reversed passive Arthus reaction induced with egg albumin-anti-egg albumin) were quantitated and the kinetics of the various vascular phenomena were ascertained. Hyperemia, increase in vascular permeability, platelet accumulation, and polymorphonuclear (PMN) leukocyte accumulation occurred relatively early after induction of the inflammatory lesions, and peaked in 2-4 h. Hemorrhage peaked in 6-h-old lesions. Morphological studies confirmed that almost all infiltrating cells were PMN leukocytes and immunofluorescent tracer studies showed immune complexes in vessel walls as early as 15 min after i.v. injection of the fluoresceinated antigen and the intradermal injection of antibody. By 8 h the progression of the lesions had subsided and by 24 h there were signs of resolution. A pathway for the development of the inflammatory lesions induced with immune complexes is proposed.

Animals↗
PubMed1982

The characterization of lymphocytes migrating through chronically inflamed tissues.

Afferent lymphatics draining Freund's adjuvant-induced granulomas and efferent lymphatics from normal subcutaneous lymph nodes were cannulated in sheep. It was previously reported that cells collected from these lymphatics, after being radiolabelled with 111In and returned to the animal intravenously, migrated from the blood back through the granuloma or lymph node into the lymph compartment from which they were originally obtained. Afferent lymph cells preferentially migrated out of the circulation in the granuloma rather than the lymph node. The cell responsible for this selective migration was found to be a small recirculating T lymphocyte. Macrophages and lymphoblasts did not demonstrate this migration. Similarly, B cells did not contribute to the lymphocyte migration observed. The migration of lymphocytes through normal uninflamed skin was examined. Afferent cells migrated through normal skin in the same way as through a granuloma, suggesting that neither antigen nor local inflammatory changes were responsible for this migration.

Animals↗
PubMed1982

The appearance and significance of phospholipase A2 in lymph draining tuberculin reactions.

Popliteal and prefemoral lymphatics of sheep were cannulated, and lymph was collected before and during the course of responses to PPD and concanavalin A. Hyperemia-inducing activity (HIA) and phospholipase A2 (PLA2) were released into lymph in response to antigenic stimulation, whereas lymph plasma draining unstimulated lymph nodes had consistently little or no detectable HIA and PLA2 activity. HIA appeared in the lymph efferent to the stimulated node at a time when blood flow to the responding node was enhanced. While the appearance of HIA did not directly correlate with changes in lymphocyte output, lymph protein concentration, or lymph flow rates, there was, however, a statistically significant correlation between HIA and PLA2 levels in lymph plasma, suggesting that extracellular PLA2 may contribute to the vasoactivity in lymph and thereby modulate blood flow to areas of antigenic stimulation. Vasoactive lymph, injected into rabbits, induced hyperemia via an indomethacin-sensitive pathway, since the induction of hyperemia was abrogated by pretreatment of injection sites with indomethacin. The extracellular release of PLA2 in response to inflammatory stimuli may represent an amplification mechanism for the generation of high levels of prostaglandins found in lymph draining stimulated nodes.

Animals↗
PubMed1982

The production of plasminogen activator by afferent but not efferent lymph cells emigrating from chronic granulomatous lesions in sheep.

Subcutaneous granulomas were induced in sheep by injecting Freund's adjuvant. At varying times thereafter afferent and efferent lymphatics draining the granulomas were cannulated. Lymph was collected for periods up to several days or weeks from either normal skin or from inflammatory lesions 15 to 120 days after the initiation of the lesions. The fibrinolytic activity of cells and cell culture medium in which cells were grown was assayed by using 125I-fibrin plates. No detectable enzyme activity was found from normal afferent, normal efferent, or stimulated efferent lymph cells. Afferent granuloma cells produced a plasminogen-dependent, DFP inhibitable protease activity that was dependent on the cell concentration and the incubation time. Results of cell separation techniques such as sedimentation velocity, adherence on fibrin plates, and Sephadex G-10 fractionation showed that the large, macrophage-like cell population in afferent lymph was secreting the plasminogen activator. The lymph cells collected from lesions 1 to 2-mo-old were more active than an equivalent number of cells collected from earlier or later lesions. When tuberculin was injected directly into lesions the lymph cells that appeared in the subsequent 1 to 2 days produced more enzyme per cell. The relationship between plasminogen activator and other possible mediators that appear in either the cells or plasma of afferent lymph is discussed.

Animals↗
PubMed1981

Lymphocyte traffic through chronic inflammatory lesions: differential migration versus differential retention.

Afferent lymphatics draining granulomas and efferent lymphatics from normal lymph nodes were cannulated in sheep. Cells collected from these lymphatics were radiolabelled in vitro with 111In (afferent lymph cells) and 51Cr (efferent lymphocytes) and both labelled cells were returned to the animal simultaneously by i.v. injection. The reappearance of these labelled cells in lymph, and the amount of 111In and 51Cr in normal or antigenically stimulated lymph nodes, cutaneous inflammatory sites (FCA-granulomas, NLT- and BCG-induced lesions) and blood was determined 24 hr later. As previously reported, labelled afferent cells preferentially migrated from the blood back through the granuloma into afferent lymph, and efferent lymphocytes back into efferent lymph. Forty per cent as many 111In- as 51Cr-labelled cells ;appeared in efferent lymph. This was caused by the greater migration of 51Cr-labelled cells appeared in efferent lymph. This was caused by the greater migration of 51Cr- than 111In-labelled cells out of the blood into the node. Neither cell type was selectively retained in the node, and 28% of the labelled cells that entered the node migrated on into efferent lymph in 24 hr. Similarly, there was no selective retention of either cell type in the granuloma, and equal amounts of 111In the 51Cr appeared in afferent lymph. The ratio 111In/51Cr in the blood suggested that in the lymph node the two labelled cell populations were extracted equally, while in the granuloma selectively at the level of the vascular endothelium resulted in the preferential extraction of 111In-labelled (afferent lymph) cells.

Animals↗
PubMed1980

Feto-maternal histoincompatibility and placental blood flow.

1. We have designed experiments aimed at resolving some of the controversy concerning the effect of histoincompatibility on the development of the fetus and its placenta. 2. Experiments included the generation of pregnancies in which H-2 compatible and H-2 histoincompatible embryos were simultaneously present. Genetic markers (Brachyury and Kink) were used to facilitate determination of the H-2 haplotype. Additional strain combinations were used to analyse the role of non-H-2 differences. 3. In addition to determining fetal and placental weights, blood flow to the placenta was measured by use of radioisotope-labelled microspheres introduced into the arterial circulation. 4. Under the conditions of our experiments we have failed to detect differences in fetal weight, in placental weight, or in placental blood flow. 5. Thus we support the increasingly prevalent view that histo-incompatibility does not necessarily lead to changes in placental or fetal weight, and we add the additional finding that placental blood flow also is not significantly altered as a result of feto-maternal incompatibility.

Animals↗
PubMed1980

Secretion of a hyperemia-inducing moiety by mitogen or glycogen stimulated mononuclear inflammatory cells of sheep and rabbit.

A nonlymphokine mediator of hyperemia has been shown to be secreted by both rabbit peritoneal exudate cells stimulated with 5% glycogen and by concanavalin A treated cells from afferent lymph of sheep. This mediator is not stored in an active form in cells, but is either activated or synthesized de novo in response to antigenic or mitogenic stimuli. Secretion of the mediator is inhibited by culturing cells in the presence of dexamethasone but not indomethacin. However, expression of the activity is inhibited by pretreatment of the assay animals with indomethacin, suggesting a two-step induction of hyperemia. A similar mediator was found to be secreted by sheep and rabbit alveolar lavage cells, and rat peritoneal exudate cells. The presence of this hyperemia-inducing activity from diverse species suggests a fundamental role in controlling blood flow. Alteration of blood flow may modulate delivery of blood-borne cells and factors to sites of chronic inflammation.

Animals↗
PubMed1980

The distribution of prostaglandins in afferent and efferent lymph from inflammatory sites.

Arachidonic acid labeled with (14)C was injected directly into lymph nodes that had been stimulated at various times with Escherichia coli. The efferent lymph was collected, and labeled catabolites were extracted and analyzed chromatographically. The pimary conversion product recovered was Prostaglandin E(2) (PGE(2)), with the lesser products thromboxane, prostacyclin and prostaglandin F(2alpha) (PGF(2alpha)) also detected. When the efferent lymph was analyzed by radioimmunoassay after subcutaneous injectino of E coli into the hock, PGE and PGF levels rapidly increased, reached the highest levels in the first 10 hours, and then returned to normal by 24 hours. When the afferent lymph plasma draining inflammatory sites was compared directly with efferent lymph, PGF levels were similar, but the PGE level was always several times higher in the afferent lymph. To examine the catabolism of PG, either (3,)H-PGF(2alpha) of (3)H-PGE(2) was injected into the node, and the efferent lymph plasma was analyzed. No conversion of PGF(2alpha) to other products was found. In contrast, catabolic products of PGE(2) were detected. With the use of equilibrium dialysis techniques, the binding of PGE(2) and PGF(2alpha) to proteins in lymph and to bovine serum albumin (BSA), human serum albumin (HSA), and BSA stripped of its fatty acids was established. The binding to lymph proteins correlated with the albumin concentrations in the lymph. This albumin binging probably facilitated the retention and transport of PG in the lymph. PG appears in the lymph at a time corresponding to the uptake and processing of antigen by the node and near the time when lymphokines are detected in lymph and could modulate several steps in the immune response. The PGE detectable in the lymph draining an inflammatory site may play a role in the modulation of blood flow.

Animals↗
PubMed1980

Measurement of lymphocyte traffic with indium-111.

This study was designed to assess the use of 111indium as a radioactive marker for the investigation of lymphocyte recirculation in the sheep. Lymphocytes were collected from sheep with indwelling catheters in the efferent lymphatic ducts of peripheral lymph nodes and labelled with 111In-oxine or Na2 51CrO at doses of 10 microCi and 50 microCi/10(8) cells respectively. After intravenous injection the lymphocyte specific activity (c.p.m./10(7) cells) in blood and lymph was measured for several days. The maximum specific activity in efferent lymph was twelve-fold greater with 111In than with 51Cr-labelled cells. The kinetics of lymphocyte traffic as measured in double labelling experiments was very similar. The modal transit time was 21.6 hr with each isotope. The recovery of 111In-labelled cells was not significantly different from cells labelled with 51Cr. In vivo viability of the labelled cells was further supported by the normal proliferative response observed with 111In-labelled lymphocytes compared to unlabelled cells in the normal lymphocyte transfer reaction. In conclusion, 111In-oxine is an excellent radioactive label for lymphocytes in the sheep. Because of its high counting efficiency and cell labelling characteristics one can label as few as 10 million lymphocytes, or a subpopulation of cells, and assess their recirculation.

Animals↗
PubMed1980

A comparison of lymphocyte migration through intestinal lymph nodes, subcutaneous lymph nodes, and chronic inflammatory sites of sheep.

The migration of 51Cr- and 111In-labeled lymphocytes from blood to various lymph compartments was studied in sheep. When lymphocytes were isolated from lymph, radiolabeled, and returned intravenously to the same animal, nonrandom patterns of lymphocyte migration were observed, which depended on the source of the labeled cells. Lymphocytes isolated from intestinal (jejunum, ileum, or ileocecal junction) efferent lymph always produced greater specific activity in the efferent intestinal lymph than in the efferent lymph of subcutaneous (popliteal or prefemoral) lymph nodes. Conversely, lymphocytes isolated from the efferent lymph of subcutaneous lymph nodes produced greater specific activity in the efferent lymph of subcutaneous lymph nodes than in the intestinal efferent lymph. Unit gravity sedimentation of the free-floating lymphocytes in intestinal efferent lymph demonstrated that small, recirculating lymphocytes, but not lymphoblasts, were responsible for the radioactivity recovered in lymph. The most dramatic examples of nonrandom lymphocyte migration were seen when the migration of lymphocytes was compared between the intestinal efferent lymph and through sites of chronic inflammation.

Animals↗
PubMed1979

The migration of lymphocytes in the fetal lamb.

The migration of 51Cr-labeled autologous lymphocytes from intestinal or prescapular lymph was compared in fetal lambs and adult sheep. A subpopulation of lymphocytes present in intestinal lymph of adults which migrated to the small intestine was not found in fetal intestinal lymph. There were marked differences in the migration of fetal and adult lymphocytes to the lungs and liver. In spite of the absence of circulating antibodies or immunoglobulins and of extrinsic antigen in the immunologically virgin sheep fetus, the circulation of lymphocytes through the spleen and lymph nodes of fetal lambs was more intense than in the adult.

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