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Biomedical subjects

E J Goetzl

Publications and source records attributed to E J Goetzl.

At least 181 records · Page 10Linked to original sources
PubMed1984

Regulation of epithelial electrolyte transport by metabolites of arachidonic acid.

Intestine (both small and large) secretes chloride in response to prostaglandins and agents, such as bradykinin, that increase prostaglandin synthesis. The colon, but not the small intestine, can also be stimulated to secrete chloride by certain lipoxygenase products, such as 5-hydroperoxy-eicosatetraenoic acid and 5-hydroxy-eicosatetraenoic acid, but not by leukotrienes. Intestine generates these compounds and leukotriene B4 (but not C, D, and E) and their synthesis is increased by melittin, calcium ionophore A23187, and bradykinin.

Animals↗
PubMed1984

Recognition of leukotriene B4 by a unique subset of human T-lymphocytes.

Leukotriene (LT) B4, but not 12(S)-LTB4 or LTC4, inhibits the generation of lymphokine-designated leukocyte inhibitory factor by purified human T-lymphocytes. LTB4 coupled to fluorescein-labeled human serum albumin interacts specifically with approximately 11% of the T-lymphocytes as assessed by fluorescence-activated flow cytometry. The LTB4-reactive T-lymphocytes are distributed between the suppressor-cytotoxic (14%) and helper-inducer (8%) subsets, which were identified concurrently by phycoerythrin-labeled monoclonal antibodies to subset-specific antigens. LTB4, but not 12(S)-LTB4 or LTC4, significantly enhances the proliferation of mitogen-stimulated purified suppressor-cytotoxic T-lymphocytes at concentrations of 10(-12)M to 10(-6)M and significantly inhibits the proliferation of mitogen-stimulated purified helper-inducer T-lymphocytes at concentrations of 10(-8)M to 10(-6)M, as assessed by the uptake of [3H]thymidine. The net effect of LTB4 on blood T-lymphocytes is immunosuppression that may be expressed in some human hypersensitivity and inflammatory diseases.

Antigens, Surface↗
PubMed1984

Human T-lymphocyte subset specificity of the regulatory effects of leukotriene B4.

Leukotriene B4, but not (12S)-leukotriene B4, coupled to fluorescein-labeled human serum albumin interacts specifically with human T lymphocytes, as assessed by fluorescence-activated flow cytometry. Approximately 11% of blood T lymphocytes bind the fluorescent conjugate of leukotriene B4. The leukotriene B4-reactive T lymphocytes are distributed between the suppressor-cytotoxic (14%) and helper-inducer (8%) subsets, which were identified concurrently by phycoerythrin-labeled monoclonal antibodies to subset-specific antigens. Leukotriene B4, but not (12S)-leukotriene B4 or leukotriene C4, enhances significantly the proliferation of mitogen-stimulated purified suppressor-cytotoxic T lymphocytes, at concentrations of 10(-12) M to 10(-6) M, and inhibits significantly the proliferation of mitogen-stimulated purified helper-inducer T lymphocytes, at concentrations of 10(-8) M to 10(-6) M, as assessed by the uptake of [3H]thymidine. The net effect of leukotriene B4 on blood T lymphocytes is immunosuppression, which may be expressed in some human hypersensitivity and inflammatory diseases.

Antibodies, Monoclonal↗
PubMed1984

Defective polymorphonuclear leukocyte chemotaxis in homosexual men with persistent lymph node syndrome.

Persistent lymph node syndrome, epidemiologically related to acquired immune deficiency syndrome, is characterized by reactive lymphadenopathy and an increased incidence of localized bacterial, viral, and fungal infections. Seven typical patients were found to have a localized infection every 4.5 +/- 2.0 months (mean +/- SD) since onset of adenopathy. Because recurrent bacterial infections may be associated with defective polymorphonuclear leukocyte (PMNL) function, studies of PMNL function in these patients were undertaken. The patients' PMNLs had diminished chemotactic responses to high concentrations of two structurally distinct chemotactic factors, leukotriene B4 and N-formylmethionylleucylphenylalanine. The patients' PMNLs also had deficient degranulating responses to the former but not to the latter. Diminished PMNL function may contribute to the observed increased incidence of localized infections, which are a major source of morbidity, in these patients.

Adult↗
PubMed1984

Substance P recognition by a subset of human T lymphocytes.

The interaction of substance P with human blood T-lymphocytes, which stimulates T-lymphocyte proliferation, was quantified by both flow cytometric and direct binding assays. Fluorescence-detection flow cytometry recorded the binding of dichlorotriazinylamino-fluorescein-labeled substance P to 21 +/- 10% (mean +/- SD, n = 6) and 35 +/- 8% (n = 2) of human blood T-lymphocytes before and after stimulation with 10 micrograms/ml of phytohemagglutinin, respectively. The suppressor-cytotoxic (leu 2a) and helper-inducer (leu 3a) subsets identified by phycoerythrin-labeled monoclonal antibodies contained substance P-reactive T-lymphocytes at respective mean frequencies of 10 and 18%. [3H]substance P bound rapidly and reversibly to a mean of 7035 +/- 2850 sites/T-lymphocyte, which exhibited a dissociation constant (KD) of 1.85 +/- 0.70 X 10(-7) M (mean +/- SD, n = 5). [D-Pro2,D-Phe7,D-Trp9]substance P inhibited the binding of dichlorotriazinylamino-fluorescein-labeled substance P and [3H]substance P to T-lymphocytes at concentrations that suppressed the proliferative response to substance P. Substance P, eledoisin, and substance K (alpha-neurokinin), which all share with substance P the carboxy-terminal substituent -Gly-Leu-Met-NH2, were more potent than substance P in inhibiting the binding of [3H]substance P to T-lymphocytes, suggesting the importance of this sequence in the interaction. Purified human blood B-lymphocytes, monocytes, polymorphonuclear leukocytes, and platelets, and cultured Hut 78 cutaneous lymphoma T-cells, Jurkat cells, Molt-4 lymphoblasts, and HL-60 and U-937 monocyte-like cells all showed only minimal specific binding of [3H]substance P. The recognition of substance P by T-lymphocytes provides one mechanism for selective modulation of immunity by sensory nerves.

Binding, Competitive↗
PubMed1984

Circulating eosinophil colony-forming cells in pure eosinophil aplasia.

Using a methylcellulose clonal culture method, we found eosinophil colony-forming cells in the blood of two patients: a 46-year-old white woman with a long history of urticaria and allergic rhinitis and complete absence of eosinophils secondary to IgG-mediated and complement-mediated destruction of her eosinophils; and a white woman with a history of allergic rhinitis and asthma and a complete absence of eosinophils in her peripheral blood. Addition of the patients' plasma or IgG to cultures of peripheral blood mononuclear cells derived from normal persons or the patients inhibited formation of eosinophil colonies without influencing colony formation in other hemopoietic cell lineages. In contrast, normal plasma or IgG had no effect on the formation of eosinophil colonies. That the IgG-mediated cytotoxic activity of eosinophils prevents the expression of an apparently normal eosinophilopoietic potential suggests an autoimmune basis for the eosinophil aplasia.

Agranulocytosis↗
PubMed1984

Stereospecific receptors for substance P on cultured human IM-9 lymphoblasts.

The neuropeptide substance P (SP), which has been demonstrated to bind specifically to human blood T lymphocytes and to stimulate their uptake of [3H]thymidine and [3H]leucine, now is shown to bind stereospecifically to cultured human lymphoblasts of the IM-9 line. The specific binding of [3H]SP by IM-9 lymphoblasts increases linearly with the concentration of IM-9 lymphoblasts, achieves a plateau after approximately 15 to 20 min at 4 degrees C and 4 to 6 min at 37 degrees C, and is rapidly reversible at both 4 degrees C and 37 degrees C. The binding of [3H]SP at steady-state conditions demonstrates a dissociation constant (KD) of 0.65 +/- 0.19 nM (mean +/- SD, n = 5) and 22,641 +/- 6143 receptors per IM-9 lymphoblast. Maximal specific binding of [3H]SP to IM-9 lymphoblasts is observed at pH 7.4 and is dependent on the presence of Mg2+, but not Ca2+, in the medium. The peptide structural determinants of the inhibition of binding of [3H]SP to IM-9 lymphoblasts by substituent peptides and homologs of SP indicate that the receptors recognize predominantly the carboxy-terminal portion of SP. The characteristics of the interaction of SP with IM-9 lymphoblasts suggests a receptor-directed mechanism by which neuropeptides may modulate specifically the contributions of lymphocytes to immunity.

Binding, Competitive↗
PubMed1984

A basophil-activating factor from human T lymphocytes.

Human T lymphocytes stimulated with phytohaemagglutinin (PHA) or streptokinase-streptodornase (SK-SD) generate an activity which elicits non-cytotoxic histamine release from human basophils. Filtration of the T lymphocyte-derived activity on columns of Sephadex G-100 and Fractogel 55F sequentially revealed one predominant basophil-activating factor of mol. wt. 70,000-90,000, that was designated BAF-T. BAF-T was composed of two acidic proteins of approximate pI 4.4 and 5.2-5.5, as assessed by isoelectric focusing. The distinction of BAF-T from IgE was confirmed by the failure of BAF-T to bind to an anti-IgE affinity column and the capacity of BAF-T to release histamine maximally from basophils desensitized to IgE-dependent stimuli. The inability of BAF-T to release histamine from human lung mast cells and dog cutaneous mastocytoma cells suggests target cell specificity. The source and activity of BAF-T are consistent with a specific contribution of this mediator to human cellular immune and hypersensitivity responses involving T lymphocytes and basophils.

Basophils↗
PubMed1984

Inhibition by somatostatin of the release of mediators from human basophils and rat leukemic basophils.

The release of mediators from unpurified human basophils challenged with anti-human myeloma IgE serum was suppressed significantly by somatostatin at respective concentrations of 3 x 10(-13) M to 10(-9) M for histamine and 10(-13) M to 10(-11) M for leukotriene D4, which had no effect on release elicited by ionophore A23187. A direct effect of picomole-nanomole concentrations of somatostatin on basophils predominated, as shown by the significant inhibition of immunologically stimulated mediator release from monocyte-free human basophils of 15 to 32% purity and from rat basophil leukemia cells. The dependence of basophil inhibition on the conformation of somatostatin was suggested by the lower potency of reduced and alkylated somatostatin and the lack of inhibitory activity of [D-Trp8] somatostatin. Somatostatin thus may mediate suppressive effects of sensory nerves in some basophil-dependent hypersensitivity reactions.

Animals↗
PubMed1984

Generation of a unique fibroblast-activating factor by human monocytes.

Purified human monocytes incubated with phytohemagglutinin (PHA), bacterial lipopolysaccharide (LPS), or serum-opsonized zymosan particles (OZ) generate human dermal fibroblast-activating activity, as assessed by increased fibroblast incorporation of [3H]-thymidine. A maximum concentration of fibroblast-activating activity was attained within 4 hr with OZ, whereas similar maximum levels required 12 hr with LPS and PHA. Sonicates of unstimulated monocytes had only minimal activity and the protein synthesis inhibitor cycloheximide suppressed significantly the appearance of fibroblast-activating activity, suggesting that the factors are generated prior to release. Filtration of supernates from OZ-stimulated monocytes on Sephadex G-75 yielded polydisperse fibroblast-activating activities, of which the major factors exhibited a mol. wt. of approximately 60,000 and 10,000. The supernates from PHA-stimulated monocytes had one predominant factor, termed fibroblast-activating factor of monocytes (FAF-M), with an apparent mol. wt. of 38,000 and a minor activity with a mol. wt. of 10,000. FAF-M was composed of two principles with isoelectric points of 5.1-5.2 and 4.0-4.2 and was free of interleukin-1, as determined by the absence of thymocyte-activating activity. FAF-M and other fibroblast-activating factors may contribute to wound healing and fibrosis in lesions characterized by mononuclear phagocyte infiltrates.

Adult↗
PubMed1983

Human neutrophil chemotactic and degranulating activities of leukotriene B5 (LTB5) derived from eicosapentaenoic acid.

Leukotriene B4 exhibited 10- to 30-fold greater chemotactic potency for human neutrophils than eicosapentaenoic acid-derived leukotriene B5, as assessed in modified Boyden micropore filter chambers. In contrast, leukotrienes B4 and B5 were equipotent stimuli of human neutrophil lysosomal degranulation in vitro, as quantified by the release of beta-glucosaminidase. Analyses of competitive inhibition of the binding of [3H] leukotriene B4 to neutrophils indicated that leukotriene B4 binds with a 500-fold greater association constant than leukotriene B5 to a subclass of high-affinity receptors, which appears to transduce chemotactic responses efficiently, while leukotrienes B4 and B5 bind equally well to low-affinity receptors.

Chemotaxis, Leukocyte↗
PubMed1983

Stimulus specificity of the generation of leukotrienes by dog mastocytoma cells.

Isolated dog mastocytoma cells sensitized with dog anti-ragweed IgE and challenged with ragweed antigen or incubated with ionophore A23187 or the carboxy-terminal dodecapeptide of platelet factor 4, PF4(59-70), release histamine and concurrently generate leukotrienes B4, C4, and D4. In contrast, the exposure of mastocytoma cells to 0.1-3 micrograms/ml of 15-hydroxyeicosatetraenoic acid (15-HETE) stimulates selectively the generation of leukotrienes, in the absence of histamine release, while 0.1-1 micrograms/ml of compound 48/80 releases histamine without enhancing the generation of leukotrienes. That natural stimuli are capable of selectively activating one synthetic or secretory compartment of mast cells suggests that separate subsets of receptors as well as different biochemical events may serve to mobilize each class of mediators.

Allergens↗
PubMed1983

Selective generation of leukotriene B4 by tracheal epithelial cells from dogs.

The incubation of suspensions of canine tracheal epithelial cells of greater than 95% purity with arachidonic acid (25-200 micrograms/ml) for 60-120 min resulted in the generation of a maximum of 36.2 +/- 9.1 picomoles of leukotriene B4/10(6) cells, less than 2.0 picomoles of leukotrienes C4, D4, and E4/10(6) cells, and 1030 +/- 463, 767 +/- 500, and 324 +/- 100 picomoles/10(6) cells of 15-, 12-, and 5-hydroxy-eicosatetraenoic acids, respectively (mean +/- SEM, n = 8). The identity of leukotriene B4 was established by chromatographic and spectral properties, by reactivity with mono-specific anti-plasma, and by the chemotactic activity for neutrophils. Thus, the epithelium may be an important source of mediators of inflammation and hypersensitivity of pulmonary airways.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1983

A sensitive and specific radioimmunoassay for leukotriene C4.

A sensitive and specific radioimmunoassay suitable for direct measurement of leukotriene C4 was developed. Acetylated leukotriene C4 was coupled to polyamino bovine serum albumin using 1-ethyl-3-(3-dimethylamino-propyl) carbodiimide hydrochloride as coupling agent. The conjugate in complete or incomplete Freund's adjuvant was injected into New Zealand white rabbits. At a final antiplasma dilution of 1 : 1050 the lowest detection limit of leukotriene C4 was 0.046 pmol. The antiplasma cross-reacted less than 1% with leukotrienes D4, E4 and F4, while high relative cross-reaction (86-100%) was obtained with leukotrienes C3, C5 and 11-trans leukotriene C4. In experiments where known amounts of leukotriene C4 were added to leukocyte suspensions, 67-100% of the added amount was recovered by the method. The radioimmunoassay was used to study leukotriene C4 formation after stimulation of leukocyte suspensions with the ionophore A23187.

Antibody Specificity↗
PubMed1983

Stimulation of histamine release from human basophils by human platelet factor 4.

Human basophils were stimulated to release histamine noncytotoxically by purified human platelet factor 4 (PF4) and the synthetic substituent peptide PF4(59-70). Histamine release was augmented significantly by 10(-7) M PF4 and 10(-5) M PF4(59-70), increased in a concentration-dependent manner, and attained a maximum at 3 X 10(-5) M PF4 and 3 X 10(-4) M PF4(59-70) similar to that achieved by goat anti-human myeloma IgE. PF4 (1-60) failed to initiate the release of histamine, which confirmed that the critical determinant of activity is in the carboxy-terminal sequence. Histamine release from basophils by optimally effective concentrations of PF4 and PF4(59-70) reached a plateau by 1-3 min, as contrasted with 10 min or longer for anti-IgE. The elimination of calcium and magnesium from the buffer suppressed the release of histamine by anti-IgE by 79-83%, but had no effect on that elicited by PF4(59-70). The rate of uptake of [125I]PF4 by purified basophils was similar on a molar basis to the rate of release of histamine by the same concentrations of PF4. The noncytotoxic release of histamine from human basophils by PF4 thus is temporally and biochemically distinct from that mediated by IgE and may be similar to that evoked by other polycationic stimuli.

Antibodies, Anti-Idiotypic↗
PubMed1983

Platelet-derived growth factor stimulates mouse 3T3 cell mitogenesis and leukocyte chemotaxis through different structural determinants.

Platelet-derived growth factor (PDGF) stimulates both proliferation of fibroblasts and chemotaxis of leukocytes. In this study we compared the mitogenic and chemotactic activities of native PDGF and reduced PDGF. Reduction of PDGF (Mr = 32,000) to its constituent polypeptides (Mr = 14,000 and 17,000) caused a loss of the ability to stimulate proliferation of Balb/c 3T3 cells. However, reduced PDGF retained virtually all of its activity as a chemotactic agent for human neutrophils and monocytes. A half-maximal chemotactic response to both native and reduced PDGF occurred at a concentration of approximately 0.08 nM for neutrophils and 0.1 nM for monocytes. The maximal chemotactic response to reduced PDGF was at least as great as the maximal response to native PDGF. Both native and reduced PDGF stimulated the release of the lysosomal enzyme, beta-glucosaminidase, from neutrophils with a half-maximal response at less than 0.1 nM. However, the net maximum release of this enzyme by PDGF (and reduced PDGF) was significantly less than that stimulated by a maximal concentration of the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine. These results indicate that different structural determinants are required for the proliferative response of 3T3 cells to PDGF and for the chemotactic response of leukocytes to PDGF.

Animals↗
PubMed1983

Enhancement of human neutrophil adherence by synthetic leukotriene constituents of the slow-reacting substance of anaphylaxis.

The functionally predominant constituents of the slow-reacting substance of anaphylaxis (SRS-A), designated leukotrienes C4 and D4 (LTC4 and LTD4), as well as the leucocyte chemotactic factor leukotriene B4 (LTB4) enhance the adherence of human neutrophils to Sephadex G-25. Enhancement of neutrophil adherence was significant at leukotriene concentrations of 3 X 10(-9) M -3 X 10(-7) M, and reached a maximum level for each of the leukotrienes that was similar in magnitude to that evoked by the neutrophil chemotactic peptide N-formyl-methionyl-leucylphenylalanine (FMLP). The leukotrienes and FMLP elicited optimum increases in neutrophil adherence within 1-2 min at 37 degrees. Indomethacin inhibited the increase in neutrophil adherence evoked by LTC4 and LTD4 and the concurrent elevation in the concentration of endogenous thromboxane B2. The smooth muscle contractile and vasoactive factors LTC4 and LTD4, which lack chemotactic activity for leucocytes, are as active as LTB4 in stimulating human neutrophil adherence, and the effect may be mediated in part by neutrophil-derived thromboxane A2.

Arachidonic Acids↗