Search PubMed⌕ Search

Biomedical subjects

E J Goetzl

Publications and source records attributed to E J Goetzl.

At least 253 records · Page 14Linked to original sources
PubMed1980

The human PMN leukocyte chemotactic activity of complex hydroxy-eicosatetraenoic acids (HETEs).

The lipoxygenation of arachidonic acid in basophils, mastocytoma cells, and other leukocytes generates the unstable intermediate 5-hydroperoxy-eicostaetraenoic acid, which is converted in part to a series of complex hydroxy-eicosatetraenoic acids (HETEs) with additional polar substituents and 3 conjugated double bonds. One of the products, 5,12-di-HETE, is chemotactic for human neutrophils in vitro at a concentration as low as 3 ng/ml and evokes a maximal neutrophil chemotactic response at 30 ng/ml, as compared to 1000 ng/ml for 5-HETE and 10,000 to 20,000 ng/ml for 11-HETE and 12-HETE. In contrast, other products in the same series, such as the slow reacting substance 5-hydroxy-6-glutathionyl-eicosatetraenoic acid (leukotriene C), and the platelet-derived 8,9,12-trihydroxy-eicosatrienoic acid and 8,11,12-trihydroxy-eicosatrienoic acid exhibited only marginal neutrophil chemotactic activity. Only 5,12-di-HETE released significant quantities of beta-glucuronidase and lysozyme from the neutrophils, but the maximal level of enzyme release was far less than that for the chemotactic fragment of C5 and the formyl-methionyl peptides.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1980

A novel eosinophil chemotactic factor derived from a histiocytic lymphoma of the central nervous system.

An eosinophil chemotactic activity was identified in extracts of tumour tissue and cerebrospinal fluid from a patient with a histiocytic lymphoma of the brain and spinal cord that was infiltrated extensively with eosinophils and associated with peripheral blood eosinophilia. The histiocytic lymphoma-derived eosinophils chemotactic factor, termed ECF-HL, exhibited a mol. wt of 13,000-14,000 by filtration on Sephadex G-50, was highly acidic based on its elution from a high pressure anion exchange column at pH 2 x 3 - 2 x 1, and was susceptible to inactivation by proteolytic digestion. ECF-HL was absent from extracts of control human brain tissue, glioblastomas, other lymphomas and a variety of carcinomas that lacked an accumulation of eosinophils. Partially purified ECF-HL had no chemokinetic activity, but rendered eosinophils unresponsive to other chemotactic factors. Thus ECF-HL is structurally and functionally distinct from other recognized peptides that are preferentially chemotactic for eosinophils.

Adult↗
PubMed1979

Generation of unique mono-hydroxy-eicosatetraenoic acids from arachidonic acid by human neutrophils.

Incubation of [3H]arachidonic acid with the 17,000-g supernatant from homogenates of human neutrophils in the presence of indomethacin generated the unique metabolites 9-OH-5,7,11,14-eicosatetraenoic acid (9-HETE) and 8-HETE, in addition to 12-HETE, 11-HETE and 5-HETE. The human neutrophil chemotactic activity of the HETE products exhibited a rank-order of potency with 5-HETE greater than 8-HETE = 9-HETE greater than 11-HETE = 12-HETE. The expression of chemokinetic activity as well as chemotactic activity suggested that the endogenous production of these principles may influence the mobility of human neutrophils.

Arachidonic Acids↗
PubMed1979

Unique characteristics of superoxide production by human eosinophils in eosinophilic states.

Eosinophils from patients with peripheral blood eosinophilia and human neutrophils from normal subjects and patients with neutrophilia produced superoxide anion (O2-) in vitro at similar rates in the absence of stimulation and exhibited comparably increased rates of O2- production during the initial 1 h of incubation with opsonized zymosan. In the presence of opsonized zymosan, the rate of O2- production by eosinophils was constantly high for 3 h, whereas the rate of production by neutrophils fell by more than 65% after 1 h. Consequently, the amount of superoxide produced by phagocytizing leukocytes was twofold higher for eosinophils than for neutrophils at 3 h. O2- production by cell-free sonicates of zymosan-stimulated eosinophils and neutrophils exhibited the same preference for NADPH over NADH. One mM sodium azide significantly decreased the generation of O2- by phagocytizing eosinophils, but lacked an effect on neutrophils. the prolonged release of O2- by eosinophils engaged in phagocytosis may contribute both to their unique microbicidal profile and to the capacity of eosinophils to injure host tissues in some eosinophilic syndromes.

Eosinophilia↗
PubMed1979

Specific inhibition of the polymorphonuclear leukocyte chemotactic response to hydroxy-fatty acid metabolites of arachidonic acid by methyl ester derivatives.

The human polymorphonuclear (PMN) leukocyte chemotactic activity of the hydroxy-fatty acid metabolites of arachidonic acid, 12-l-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 12-l-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE), is eliminated by methylation. Both methyl esters are specific competitive inhibitors of the PMN leukotactic responses to the parent stimuli, and exert no effect on the responses to formyl-methionyl peptides or chemotactic fragments of the fifth component of complement. 50% inhibition of the in vitro chemotactic responses of PMN leukocytes to HETE and HHT was achieved by an equimolar concentration of the corresponding methyl esters, whereas reciprocal cross-inhibition was observed at molar ratios of HETE methyl ester to HHT and HHT methyl ester to HETE which reflected the three- to fivefold greater chemotactic potency of HETE relative to HHT. Methyl esters of structurally related, but nonchemotactic, fatty acids did not competitively inhibit the chemotaxis elicited by HETE or HHT. The intraperitoneal injection of HETE in guinea pigs evoked an eosinophil response at 30 min and a neutrophil response at 5 h, which were prevented by a one-to twofold molar ratio of HETE methyl ester. The competitive inhibition of the in vitro chemotactic activity and the in vivo leukotactic effect of the unsaturated hydroxy-fatty acids by homologous methyl ester derivatives suggests that the cellular component of natural inflammatory reactions may be susceptible to specific regulation by receptor-directed modulation of the activity of the predominant chemotactic principles.

Arachidonic Acids↗
PubMed1979

The immunological generation of a platelet-activating factor and a platet-lytic factor in the rat.

Antigen challenge of the rat peritoneal cavity which had been prepared with IgGa-rich antiserum generated activities which released [14C]-serotonin from pre-labelled human platelets. After adsorption of these activities onto Amberlite XAD-8 and elution in 80% ethanol, two factors of differing polarity were resolved by chromatography on diethylaminoethyl cellulose in organic solvents. The activity eluting in the 7:1 chloroform:methanol solvent contained a platelet-lytic factor (PLF) assessed by the parallel release of lactic acid dehydrogenase and [14C]-serotonin; the cytotoxicity of this fraction was confirmed by phase-contrast microscopy examination which demonstrated fragmentation of the exposed platelets. The activity eluting in the 1:1 methanol: aqueous 1.0 M ammonium carbonate solvent was a platelet-activating factor (PAF) as defined by release of [14C]-serotonin without lactic acid dehydrogenase. Both the lytic and the activating principles were separable from slow reacting substance of anaphylaxis and polymorphonuclear leucocyte chemotactic activity, and each presented a single activity peak of differing mobility when chromatographed on silica gel H plates. Human eosinophil phospholipase D inactivated the lytic factor by more than 85% in 2 h at 37 degrees without affecting the activity of the activating factor. The release of [14C]-serotonin induced by the PAF was not affected by the absence of calcium from the medium or by elevations in the platelet concentrations of cyclic AMP or cyclic GMP that resulted from pre-incubation of platelets with prostaglandin D2 or sodium ascorbate, respectively.

Animals↗
PubMed1979

Chemotactic factor receptors of human PMN leucocytes. I. Effects on migration of labelling plasma membrane determinants with impermeant covalent reagents and inhibition of labelling by chemotactic factors.

The mechanism of stimulation of human PMN leucocyte-directed migration by chemotactic factors was studied by pre-labelling plasma membrane determinants with impermeant covalent reagents and assessing the effects of such modification on spontaneous mitration and chemotaxis in modified Boyden chambers. Pre-treatment of PMN leucocytes with 10(-9) to 10(-6) M isethionyl acetimidate, which selectively labels amino groups, enhanced spontaneous migration and concomitantly inhibited chemotaxis to fragments of the fifth component of complement (C5fr), 12-L-OH-5,8,10,14-eicosatetraenoic acid (HETE) and several formyl--methionyl (f--Met) peptides to an extent that was inversely related to the magnitude of the chemotactic response of untreated PMN leucocytes. Para-chloromercuribenzene sulphonate, which selectively labels sulphydryl groups, inhibited chemotaxis to diverse stimuli without substantially influencing spontaneous migration, while the diazonium salt of sulphanilic acid, which labels several types of plasma membrane determinants, altered neither spontaneous nor chemotactic migration. Incubation of PMN leucocytes with various concentrations of [3H]-isethionyl acetimidate labelled from 33,000 amino groups per PMN leucocyte at 10(-6) M to over 800,000 at 10-4) M, a reaction that was substantially inhibited by chemotactic concentrations of C5fr and HETE, but not by f--Met peptides. Subcellular fractionation of PMN leucocytes labelled with [3H]-isethionyl acetimidate localized the radioactivity to membrane-rich fractions. Free amino groups thus appear to be functionally critical determinants of some chemotactic factor receptors on the plasma membrane of PMN leucocytes.

4-Chloromercuribenzenesulfonate↗
PubMed1979

Inhibition by non-steroidal anti-inflammatory agents of the ascorbate-induced elevations of platelet cyclic AMP levels.

Ascorbate induces a 10- to 25-fold rise in platelet guanosine 3'5'-cyclic monophosphate (cGMP) and this action is prevented or reversed by the introduction of aspirin, indomethacin, ro 5,8,11,14-eicosatetraenoic acid (TYA). The reversal was 70-90% complete at 30 s, the earliest time point that was examined. As the effect of ascorbate on cGMP was not diminished by anaerobic conditions, which inhibited the oxidation of exogenous arachidonate by more than 95%, metabolic inhibition of cyclo-oxygenase activity did not duplicate the effect of the non-steroidal anti-inflammatory agents. Ascorbate did not act by the activation of phospholipase A2 in that the ascorbate-induced evevation of cGMP was not accompanied by increased oxygen consumption or the release of [14C]-arachidonate from prelabeled platelets. Thus, despite the finding that non-steroidal anti-inflammatory agents prevent and reverse the ascorbate-mediated elevation of cGMP, it was not possible to relate their respective antagonist and agonist actions to the oxidation of arachidonate.

1-Methyl-3-isobutylxanthine↗
PubMed1978

Morphologic and functional evidence for release of mast-cell products in bullous pemphigoid.

We studied nine patients with bullous pemphigoid, a generalized cutaneous eruption- for evidence of mast-cell involvement during development of lesions. As in other reports, six of nine patients demonstrated a serum antibody directed against the epidermal basement-membrane zone. Direct immunofluorescence studies of lesions revealed depostion of immunoglobulin and complement proteins at the basement-membrane zone in six of nine and nine of nine patients, respectively. Participation of mast cells was suggested by a sequence of pathologic alterations in which there was progressive mast-cell degranulation and late eosinophil infiltration. In addition, a factor chemotactic for human eosinophils with the size and charge characteristics of the eosinophil chemotactic factor of anaphylaxis was identified in blullous fluid. The data indicate that, in addition to activation of the complement system, involvement of mast cells is an early and continuing event in the development of the cutanenous lesions of bullous pemphigoid.

Autoantibodies↗
PubMed1978

Ascorbate therapy in impaired neutrophil and monocyte chemotaxis. With atopy, hyperimmunoglobulinemia E, and recurrent infection.

A Candida albicans corneal ulcer developed in a 24-year-old man with a history of eczema, asthma, and multiple bacterial infections since childhood. The infection responded well to oral flucytosine (12 g/day for 15 days) and topical amphotericin B. Positive laboratory findings included eosinophilla, hyperimmunoglobulinemia E, and impaired neutrophil and monocyte spontaneous migration and chemotactic responses. Ascorbic acid corrected the monocyte defect in vitro and in vivo, but had no effect on neutrophil function.

Adult↗
PubMed1978

Endomyocardial disease and eosinophilia. Report of a case.

While an association between blood eosinophilia and endomyocardial disease has been recognized, the role of the eosinophil in the pathogenesis of the cardiac lesions remains uncertain. In a 69-year-old-man with large cell carcinoma of the lung, marked eosinophilia was stimulated by and progressed with the course of the neoplasm which was producing an eosinophil chemotactic factor. Peripheral blood eosinophils were vacuolated and degranulated while those in the bone marrow were morphologically normal. Clinical evidence of cardiac dysfunction developed one month prior to death. At autopsy, 12 months after the onset of symptoms, endomyocardial disease was present. There were numerous eosinophils in the damaged myocardium and surrounding the pulmonary neoplasm. In patients with endomyocardial disease and eosinophilia, the eosinophil may be directly cardiotoxic or a primary mediator of cardiac damage; therapeutic attempts to reduce the number of eosinophils might be benefit.

Aged↗