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S I Wasserman

Publications and source records attributed to S I Wasserman.

At least 37 records · Page 2Linked to original sources
PubMed1990

Histamine release from rodent and human mast cells induced by protoporphyrin and ultraviolet light: studies of the mechanism of mast-cell activation in erythropoietic protoporphyria.

We report that protoporphyrin (PP) and ultraviolet light (UVA) induces histamine release from rat peritoneal mast cells, mouse bone marrow mast cells and human cutaneous mast cells in a dose- and temperature-dependent manner. The mast-cell activation was associated with loss of membrane integrity and inhibited by the hydrogen peroxide scavenger, catalase. Histamine release was independent of extracellular calcium in the rodent mast cells, but was markedly reduced in the absence of calcium in human cells. These findings indicate that PP and UVA induce mast-cell-mediator release by a process that may involve hydrogen peroxide formation. There appear to be differences in response to PP and UVA between rodent and human mast cells.

Animals↗
PubMed1990

Immune-related intestinal chloride secretion. II. Effect of adenosine on T84 cell line.

The inflammatory mediator adenosine caused sustained Cl- secretion across monolayers of T84 cells. The effect was promptly reversed by the adenosine receptor antagonist 8-phenyltheophylline and appeared to be mediated through an adenosine A2-receptor [rank order of potency: 5'-(N-ethyl)-carboxamido-adenosine (NECA) greater than adenosine greater than (-)-N6-(phenylisopropyl)adenosine (PIA) greater than or equal to (+)-PIA]. High doses of adenosine and its analogues increased cellular adenosine 3',5'-cyclic monophosphate (cAMP) but not guanosine 3',5'-cyclic monophosphate (cGMP) or free cytosolic Ca2+. However, lower concentrations of adenosine had maximal effects on Cl- secretion with little or no effect on cAMP. In other respects, Cl- secretion resembled that induced by cAMP-mediated secretagogues such as vasoactive intestinal peptide (VIP). Addition of both low and high doses of NECA activated basolateral K+ and apical Cl- channels, exhibited synergism with Ca2(+)-mediated secretagogues, did not produce additive effects with VIP or Escherichia coli heat-stable enterotoxin, and was associated with cAMP-dependent protein kinase-mediated protein phosphorylation. The results suggest that either adenosine mobilizes an intracellular pool of cAMP that is extremely efficiently coupled to the cAMP-dependent protein kinase and is thereafter rapidly destroyed or that second messenger(s) other than cAMP, cGMP, or Ca2+ are able to activate Cl- secretion in the T84 cell line. In the latter case, such messenger(s), as yet unidentified, might represent a final common pathway for cyclic nucleotide-activated Cl- secretion.

2-Chloroadenosine↗
PubMed1990

Airway levels of mast cell-derived mediators in exercise-induced asthma.

In order to assess the role of mast cell-derived mediators in the pathogenesis of exercise-induced asthma (EIA), we completed pre- and postexercise bronchoalveolar lavage (BAL) in seven atopic subjects with EIA. The study subjects were defined as having EIA if they exhibited a greater than 15% decrease in FEV1 after completing 6 min of treadmill exercise. There were no significant differences between mean preexercise and mean postexercise mast cell-derived BAL histamine (186 +/- 67 versus 148 +/- 36 pg/ml), tryptase (4.5 +/- 2.0 versus 2.8 +/- 2.0 ng/ml), prostaglandin D2 (26 +/- 11 versus 32 +/- 25 pg/ml), or leukotriene C4 (less than 100 versus less than 100 pg/ml). In addition, mast cells present in BAL fluid after exercise contained similar amounts of cellular histamine compared with BAL mast cells obtained before exercise (preexercise BAL cellular histamine, 26.6 +/- 12.3 ng/10(6) BAL cells; postexercise BAL cellular histamine, 22.7 +/- 9.1 ng/10(6) BAL cells), indicating that depletion of preformed mast cell mediators are unlikely to account for the refractory period in EIA. This study suggests that the cellular pathogenesis of EIA (mast cell-independent) differs from current theories of the pathogenesis of extrinsic allergen-induced asthma (mast cell-dependent).

Adolescent↗
PubMed1989

Transforming growth factor-beta 1 selectively inhibits IL-3-dependent mast cell proliferation without affecting mast cell function or differentiation.

Transforming growth factor-beta 1 (TGF-beta 1) is an important regulator of cell growth, differentiation, and function. We show that TGF-beta 1 selectively inhibits IL-3-dependent mouse bone marrow derived mast cell (MBMMC) proliferation without affecting MBMMC function or differentiation. TGF-beta 1 significantly decreased [3H]thymidine uptake by IL-3-dependent MBMMC in a dose-dependent manner with 50% inhibition of proliferation occurring with a TGF-beta 1 concentration of 0.1 ng/ml. A brief (i.e., 30 min) incubation of MBMMC with TGF-beta 1 is sufficient to inhibit IL-3-induced proliferation of MBMMC (cultured in the absence of TGF-beta 1) for 24 to 48 h. The inhibitory effect of TGF-beta 1 on the IL-3-dependent proliferation of MBMMC is not cytotoxic as evident from the absence of MBMMC trypan blue staining, the retained functional characteristics of the MBMMC cultured in TGF-beta 1, and the reversibility of the TGF-beta 1 induced inhibition of IL-3 dependent MBMMC proliferation. MBMMC grown in TGF-beta 1 acutely (24 to 48 h) or chronically (7 to 14 days) do not exhibit functional differences in performed or newly generated mediator secretion (Ag/IgE or calcium ionophore A23187 induced MBMMC beta-hexosaminidase or leukotriene C4 release) from MBMMC grown in the absence of TGF-beta 1. In addition, MBMMC cultured for 2 wk in TGF-beta 1 do not show evidence of differentiation as assessed by cellular histamine content or Alcian blue/safranin staining. Thus, TGF-beta 1 is an important negative regulator of IL-3-dependent mast cell proliferation in vitro, selectively inhibiting IL-3-dependent MBMMC proliferation without affecting MBMMC function or differentiation.

Animals↗
PubMed1989

Differing effects of apical and basolateral adenosine on colonic epithelial cell line T84.

Adenosine and its agonists, 5'-(N-ethylcarboxamido)adenosine and N6-(D-2-phenylisopropyl)-adenosine, induced a sustained increase in chloride secretion when added to either the apical or basolateral aspect of monolayers of the human colonic epithelial cell line T84. Secretion was induced with identical kinetics by addition to both sides, but apical addition was less potent. The rank order of potency of the agonists on either side was consistent with the presence of an adenosine A2-receptor, but the apical and basolateral receptors differed in both their ability to stimulate increases in adenosine 3',5'-cyclic monophosphate, and their susceptibility to down-modulation by chronic exposure to 5'-(N-ethylcarboxamido) adenosine in culture.

Adenosine↗
PubMed1988

Functional and biochemical characterization of rat bone marrow derived mast cells.

The functional and biochemical characterization of rat bone marrow derived mast cells (RBMMC) confirms both species-related differences between rat and mouse bone marrow-derived mast cells (MBMMC) as well as mast cell heterogeneity in a single species. Such RBMMC have the staining characteristics of mucosal mast cells and contain the mucosal mast cell protease. The RBMMC release the preformed granule mediator beta-hexosaminidase both in response to immunologic stimulation with 200 ng Ag (net release 15.8 +/- 3.8%) and in response to 1 microM calcium ionophore A23187 (net release 21.8 +/- 6.8%). However, compound 48/80, substance P, and somatostatin did not induce mast cell degranulation. In experiments with optimal beta-hexosaminidase release, the RBMMC generated similar quantities of the newly formed arachidonic acid metabolites leukotriene C4 and PGD2 when stimulated with either Ag or calcium ionophore A23187. The RBMMC incorporate [35S]sulfate into proteoglycans consisting of 90% chondroitin sulfates and 10% heparin. The chondroitin sulfates were comprised of chondroitin 4 sulfate and chondroitin sulfate diB sulfated disaccharides in a ratio of 4/1. Although we show that RBMMC and MBMMC share a low histamine content, functional IgE receptors and unresponsiveness to cromolyn and selective secretagogues (compound 48/80, substance P, and somatostatin), we also provide evidence that RBMMC differ from MBMMC in their profile of newly generated mediators, preformed granule proteoglycan, and lack of proliferative response to mouse IL-3.

Animals↗
PubMed1988

Immune-related intestinal Cl- secretion. I. Effect of histamine on the T84 cell line.

The mast cell mediator, histamine, induces a rapid and transient increase in chloride secretion across monolayers of the human colonic epithelial cell line, T84. Threshold stimulation occurred at 3 X 10(-6) M histamine and a maximal effect at 10(-4) M. The effect was reproduced by the H1 agonists 2-methylhistamine and 2-pyridylethylamine, but not by the H2 agonists 4-methylhistamine and dimaprit, suggesting the involvement of an H1 receptor. Additionally, histamine's action was inhibited by an H1 antagonist, diphenhydramine, but not by an H2 antagonist, cimetidine. Histamine treatment increased free cytosolic calcium levels, but not those of adenosine 3',5'-cyclic monophosphate (cAMP) or guanosine 3',5'-cyclic monophosphate (cGMP). The mechanism of chloride secretion induced by histamine resembled that of carbachol, in that both 1) were associated with an increase in free cytosolic calcium, 2) had a site of activation at a basolaterally localized K+ channel, and 3) were potentiated by both cAMP- and cGMP-mediated secretagogues. These results suggest that histamine may act as an intestinal secretagogue via direct interactions with epithelial cells.

Biological Transport↗
PubMed1988

Basic mechanisms in asthma.

In summary, mast cell activation is associated with the release of chemotactic factors, enzymes, proteoglycans, and vasoactive mediators. The vasoactive mediators include the leukotrienes, prostaglandin PGD2, adenosine, PAF, and histamine. Their effects are associated with an early phase reaction. This early reaction in the airways is manifested by cough, wheeze, mucous secretion, and a short-lived bronchospastic response. The release of chemotactic factors perhaps including PAF, eosinophil-directed and neutrophil-directed mediators would be associated with the influx into the airway of a variety of leukocytes although neutrophils and eosinophils predominate. The eosinophil contains a variety of toxic materials including a major basic protein known to kill tracheal epithelial cells. The eosinophil also generates PAF and leukotrienes. It could, therefore, be responsible for a self-sustaining tissue damaging inflammatory infiltrate. And finally, there are the neutral protease enzymes whose function remains unknown. It is tempting to speculate that the vasoactive mediators cause an early phase reaction while the enzymes and chemotactic factors set up the inflammation associated with a late phase response. The clinical pertinence to this has been demonstrated by researchers who studied nonspecific bronchial reactivity in patients who have early phase reactions only as compared with those who have both early and late phase reactions to antigen bronchoprovocation. These individuals with only an early phase reaction following antigen bronchoprovocation have a lesser degree of sensitivity to histamine, ie, it requires more histamine to cause bronchoconstriction, and there is no change in their histamine threshold after their early phase response.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1987

Differential effects of protoporphyrin and uroporphyrin on murine mast cells.

To investigate the mechanisms responsible for the distinct cutaneous manifestations of erythropoietic protoporphyria and porphyria cutanea tarda, the effects of protoporphyrin (PP) and uroporphyrin (URO), the predominant porphyrins in the respective disease, on mast cells were examined. Release of preformed and generated mediators was assessed by the release of radioactivity from cells labeled with [3H]serotonin and [14C]arachidonic acid, respectively. Clinically relevant doses of PP (25-500 ng/ml) and 396-407 nm irradiation (3-16 X 10(2)J/m2) induced maximal net release of preformed mediators of 44.52 +/- 6.6 to 58.01 +/- 4.0% (mean +/- SE). In contrast, irradiation in the presence of URO (50-5000 ng/ml) resulted in less than 5% net release. [3H]Serotonin release induced by PP and irradiation was calcium-independent, and was not enhanced by phorbol 12-myristate 13-acetate, a known activator of protein kinase C. This release was suppressed by catalase, a scavenger of hydrogen peroxide. Furthermore, irradiation in the presence of PP, but not in the presence of URO, resulted in perturbation of cell membrane. Irradiation in the presence of PP also resulted in a maximal net release of generated mediators of 9.98 +/- 3.5% (mean +/- SE), whereas similar treatment in the presence of URO induced less than 0.5% net release. These results suggested that the burning, stinging, erythema, and edema experienced by patients with erythropoietic protoporphyria following sun exposure, and the lack of such findings in patients with porphyria cutanea tarda, may be explained, at least in part, by the differential effects of PP and URO on mast cells.

Animals↗
PubMed1987

The regulation of inflammatory mediator production by mast cell products.

Mast cells are prominent in the airways and have been implicated in the pathophysiology of asthma. The ability of mast cells to generate or release the vasoactive/spasmogenic mediators histamine, adenosine, PGD2, sulfidopeptide leukotrienes, and platelet-activating factor is thought relevant to immediate bronchospastic responses in association with mucus secretion and airway edema. Mast cell elaboration of chemotactic factors and release of enzymes with both tryptic and chymotryptic specificity is held responsible for later reactions in which airway inflammation is prominent and nonspecific bronchial hyperreactivity is present. Recent evidence indicates that in addition to direct effect of these mast cell products some mast cell mediators themselves modulate inflammatory mediator production. Thus, adenosine, by interacting with A2 receptors on the surface of mast cells, markedly augments mast cell release of preformed granule associated mediators. Mast cell-derived chemotactic factors, exemplified by low molecular weight eosinophil directed molecules, can induce cell specific synthesis of inflammatory lipids such as platelet-activating factor. These findings only begin to suggest the richness of possibilities for mast cell regulation of the inflammatory response and underline the reality that the inflammatory response in lung as in all tissue is extremely complex and dependent upon cell-to-cell communication for its full expression.

Animals↗
PubMed1986

The effect of complement depletion on immunologically mediated middle ear effusion and inflammation.

Immunologic injury during immune response to antigen in the middle ear cavity has been suggested to be a contributing factor in otitis media with effusion (OME). One of the mechanisms proposed involves the generation of immune complexes, with subsequent injury mediated by complement fixation. To evaluate the potential role of complement in OME, an animal model of immune-mediated middle ear effusion and inflammation was used. Antigenic challenge of the middle ear of normal, sensitized guinea pigs results in OME. This response was compared with that observed in guinea pigs whose sera were decomplemented by treatment with cobra venom factor. As compared to controls, decomplemented animals exhibited less effusion [130 (+/- 35) vs 83 (+/- 60) microliter, P less than 0.05] and inflammation in the middle ear following antigenic challenge. These results suggest that complement could play a role in the pathogenesis of OME. However, the fact that animals with severely depleted serum complement still displayed a moderate amount of effusion and inflammation indicates that other mechanisms are also involved in our model of immune-mediated OME.

Animals↗
PubMed1986

Clinical characteristics of cold-induced systemic reactions in acquired cold urticaria syndromes: recommendations for prevention of this complication and a proposal for a diagnostic classification of cold urticaria.

The acquired cold urticaria (ACU) syndromes consists of nonfamilial heterogeneous disorders characterized by urticaria, angioedema, and occasionally symptoms of hypotension after cold exposure. In a study of 50 consecutive patients with ACU syndromes, it was observed that 70% experienced cold-induced systemic reactions, most frequently with aquatic activities. Patients with ACU syndromes were categorized by their response to an experimental cold-stimulation time test (CSTT) i.e., minimum time threshold of cold stimulation required to induce a coalescent wheal. One subpopulation of patients with ACU syndromes with positive CSTTs of 3 minutes or less experienced the highest incidence (68%; 13/19) of severe systemic reactions with hypotensive symptoms after natural cold exposure. However, 32% of patients with ACU syndromes (6/19) who experienced cold-induced systemic reactions with hypotension had a negative CSTT or a positive test of greater than 3 minutes. These observations indicate that all patients with ACU with active histories of cold urticaria are at risk to develop systemic reactions to cold and should therefore refrain from participating in aquatic activities. In addition, high-risk patients should receive prophylactic medications (i.e., cyproheptadine or doxepin) that are effective in suppressing this disorder. A diagnostic classification of cold urticaria is presented. This classification permits a more specific definition of the various cold urticaria disorders that comprise the ACU syndromes.

Adolescent↗