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Biomedical subjects

M V White

Publications and source records attributed to M V White.

At least 37 records · Page 2Linked to original sources
PubMed1992

Mediators of allergic rhinitis.

Although histamine is the principal mediator of the immediate allergic reaction, other inflammatory mediators as well as neuropeptides also contribute to rhinorrhea and nasal congestion. Within minutes of exposure to allergen, mast cells produce histamine, leukotriene C4, and prostaglandin D2. A concomitant increase occurs in neuropeptides and bradykinin. In vitro mast cell activation also leads to the release of tumor necrosis factor--alpha, several interleukins, and granulocyte-macrophage colony--stimulating factor. Because all these various mediators and neuropeptides may play a role in producing rhinorrhea and congestion, antihistamines alone cannot control all of the symptoms of allergic rhinitis. However, the combination of antihistamines with topical corticosteroids can inhibit the generation, release, and activity of most if not all of the mediators potentially involved in the allergic response.

Histamine↗
PubMed1992

Human neutrophil-derived histamine-releasing activity (HRA-N) causes the release of serotonin but not arachidonic acid metabolites from rat basophilic leukemia cells.

The effects of neutrophil-derived histamine-releasing activity (HRA-N) on arachidonic acid (AA) metabolism is unknown. Human basophils exposed to HRA-N released 25% of total histamine but no leukotriene C4 (LTC4). To confirm this phenomenon, rat basophilic leukemia (RBL) cells were exposed to HRA-N as well as anti-IgE, or calcium ionophore A23187. RBL cells incubated with A23187 released 44% of available serotonin and 59 and 124 pmol/10(6) cells of prostaglandin D2 (PGD2) and LTC4, respectively. Anti-IgE stimulation resulted in 34% serotonin release and the generation of 34 pmol PGD2 per 10(6) cells and 72 pmol LTC4 per 10(6) cells. In contrast, HRA-N (2 U/ml) induced 20% serotonin release, 4 pmol PGD2 per 10(6) cells, and 0.6 pmol LTC4 per 10(6) cells. Neither increasing the dose nor the incubation time of HRA-N enhanced the generation of AA metabolite. Additionally, the spectrum of AA metabolites generated by RBL cells in response to those agents was examined by reverse-phase high-performance liquid chromatography. RBL cells stimulated with A23187 released PGD2, LTB4, and its isomers, LTC4, and 5-hydroxyeicosatetraenoic acid. In contrast, HRA-N stimulation resulted in only minimal PGD2 generation and no other discernable AA metabolites. Thus, HRA-N causes selective release of serotonin without inducing AA metabolites. These data suggest that HRA-N activates mast cells through a unique pathway.

Animals↗
PubMed1992

Effects of nedocromil sodium on allergen-induced rhinitis in humans.

Sixteen patients with allergic rhinitis were recruited into a double-blind crossover protocol studying the immediate effect of nedocromil sodium (NS) on the pattern of nasal symptoms and secretions after allergen challenge. After pretreatment with placebo or NS, allergen challenge resulted in pruritus, rhinorrhea, nasal congestion, and/or sneezing within 10 minutes in 12 of 16 subjects. Prostaglandin D2 (PGD2), a marker of mast cell degranulation, increased proportionately with symptom scores, remaining above the 95% confidence interval for 120 minutes after both pretreatments. No difference in PGD2 between the NS-treatment and placebo-treatment days was observed. Protein markers extravasated through the vasculature (albumin and IgG) or secreted by mucosal glands (lactoferrin) were assayed. Total protein, albumin, IgG, and lactoferrin all remained greater than 95% confidence interval for 100 minutes after allergen challenge in the placebo-pretreated group and 120 minutes in the NS-pretreated group. Although there appeared to be a trend for lower secretion of PGD2, albumin, and IgG in the NS-treated group, the overall differences did not achieve statistical significance. This protocol revealed that two topical 130 microliter doses of a 1% solution of NS failed to significantly reduce allergen-induced symptoms, PGD2 generation, or secretion of albumin, IgG, or lactoferrin when NS was compared with placebo. The anti-inflammatory and mast cell-stabilizing effects of NS may require more prolonged pretreatment before provocation to be effective.

Adult↗
PubMed1991

Hydrocortisone inhibits rat basophilic leukemia cell mediator release induced by neutrophil-derived histamine releasing activity as well as by anti-IgE.

We determined the ability of hydrocortisone to inhibit rat basophilic leukemia cell mediator release induced by anti-IgE and by neutrophil-derived histamine-releasing activity (HRA-N). Serotonin release induced by HRA-N and anti-IgE was inhibited by 78 +/- 5 and 70 +/- 4%, respectively (IC50 7.5 x 10(-7)M) by hydrocortisone (10(-5)M). HRA-N does not cause arachidonic acid metabolism, however, anti-IgE induced the generation of PGD2 and leukotriene (LT)C4, and the generation of both mediators was inhibited by 10(-5)M hydrocortisone (IC50 = 4.8 x 10(-7)M, and 3.6 x 10(-9)M, respectively). Inhibition required at least 5 to 6 h of hydrocortisone exposure and was maximal after 22 h. The observed effects of hydrocortisone could be reproduced by human recombinant lipocortin-I (5 x 10(-7)M). Hydrocortisone, 10(-5)M, was a less potent inhibitor of calcium ionophore A23187-mediated serotonin release and PGD2 and LTC4 generation (inhibition of 20 +/- 2, 17 +/- 10, and 37 +/- 10%, respectively). Inasmuch as A23187-induced stimulation is not dependent on receptor coupling, the enhanced ability of hydrocortisone to inhibit IgE- and HRA-N-mediated events as compared with A23187 suggests that one possible site of action of hydrocortisone may be interruption of receptor-effector signals. In the presence of arachidonic acid, hydrocortisone-treated cells released as much LTB4 and PGD2 as control cells, however, serotonin release and LTC4 generation were inhibited 50 and 55%, respectively. Thus, these data suggest that hydrocortisone has three possible sites of action: 1) inhibition of phospholipase A2 activity, 2) inhibition of glutathione-s-transferase, and 3) inhibition of serotonin release by a third mechanism, possibly by interrupting the coupling of receptor and effector systems.

Animals↗
PubMed1991

Analyses of microvascular permeability in response to mediators of immediate hypersensitivity.

Mediator-induced changes in microvascular permeability were studied in rodent skin. To monitor these changes, Evan's blue dye, iodinated rat albumin and IgG, and tritiated neutral dextran molecules having different molecular radii were used. After intradermal injections of serotonin, histamine, and bradykinin, the degree of radiolabeled tracer efflux was determined by measuring the extent of blueing and the level of radioactivity in skin biopsy specimens. Although the mediators varied in potency on a molar basis (serotonin greater than bradykinin greater than histamine), the efflux resulting from each was similar. Furthermore, kinetic studies revealed that each of these vasoactive agents caused a marked but transient increase in macromolecular permeability that lasted less than 30 minutes. To determine the pore size created and the effect of charge on the transudation of macromolecules into the interstitium, fractions of neutral [3H]dextrans with a known molecular size (average radii, 12 and 4.4 nm, respectively) were infused either singly or in combination with 125I-labeled rat albumin and/or IgG before intradermal injection of serotonin, histamine, bradykinin, or compound 48/80. Regardless of the mediator used, no differences could be demonstrated in macromolecular efflux, as indicated by either the molecular size of the charge of the tracer used. Thus, all mediators of immediate hypersensitivity reactions that were studied produce venular gaps greater than 12 nm in addition to displaying similar vasopermeable characteristics.

Animals↗
PubMed1991

Neutrophils and mast cells: nedocromil sodium inhibits the generation of neutrophil-derived histamine-releasing activity (HRA-N).

The effect of nedocromil sodium on the generation of neutrophil-derived histamine-releasing activity (HRA-N) from human peripheral blood neutrophils and on the secretory effects of HRA-N and anti-IgE on rat basophil leukemia (RBL) cells was studied. Nedocromil sodium caused dose-related inhibition of HRA-N generation by human neutrophils (10(-7) to 10(-4) mol/L; inhibitory concentration of 50%, 1.5 x 10(-8) mol/L). In contrast, the presence of nedocromil sodium had no effect on HRA-N-mediated serotonin release from RBL cells. In five experiments, with one crude and four partially purified HRA-N preparations, serotonin release from RBL cells exposed to native HRA-N or HRA-N in the presence of nedocromil sodium (10(-4) mol/L) was 28% +/- 6% and 26% +/- 5%, respectively. Similar results were found with all concentrations of nedocromil sodium studied. Preincubation of RBL cells with nedocromil sodium (10(-4) mol/L) for 0 to 60 minutes also did not affect HRA-N-mediated serotonin release. Likewise, nedocromil sodium (10(-7) to 10(-4) mol/L) had no effect on anti-IgE-induced serotonin release from RBL cells. In 10 experiments, anti-IgE alone or in the presence of nedocromil sodium (10(-4) mol/L) induced 32% +/- 6% and 32% +/- 5% serotonin release, respectively. Preincubation of RBL cells with nedocromil sodium before anti-IgE exposure had no further effect. This is the first study of pharmacologic manipulation of the generation of a histamine-releasing factor. It is hypothesized that one possible mechanism whereby nedocromil sodium protects against asthma and allergic rhinitis is through inhibition of HRA-N generation.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

The pathophysiology of rhinitis. V. Sources of protein in allergen-induced nasal secretions.

Allergic rhinitis is characterized by a profuse rhinorrhea in addition to paroxysms of sneezing, nasal congestion, and pruritus. To define better the sources of nasal secretion produced during rhinitis, nasal allergen challenges were performed on nine atopic subjects with seasonal rhinitis. A single dose of allergen was sprayed into one side of the nose, and nasal lavages were collected bilaterally for 7 hours. Nasal lavages were assayed for protein (total protein, albumin, lactoferrin, and lysozyme) and mediator (histamine and prostaglandin D2) content. Protein concentrations increased and remained elevated above baseline levels in both ipsilateral and contralateral secretions for up to 3 hours after allergen challenge. The proportion of albumin relative to total protein (the albumin percent) increased on the ipsilateral side, whereas the relative proportions of lactoferrin and lysozyme (the lactoferrin percent and lysozyme percent) increased on the contralateral side. Prostaglandin D2, but not histamine, increased selectively on the ipsilateral side. These data suggest that the ipsilateral protein secretory response is due to allergen-induced mast cell mediator release causing increased vascular permeability, whereas the contralateral protein secretory response is primarily a reflex-induced glandular secretion.

Adult↗
PubMed1990

The role of histamine in allergic diseases.

Histamine, which is stored mainly in mast cells and basophils, is a prominent contributor to allergic disease. Elevations in plasma or tissue histamine levels have been noted during anaphylaxis and experimental allergic responses of the skin, nose, and airways. Of the four cardinal signs of asthma (bronchospasm, edema, inflammation, and mucus secretion), histamine is capable of mediating the first two through its H1 receptor and mucus secretion through its H2 receptor. Of the five cardinal signs of allergic rhinitis (pruritus, mucosal edema, sneezing, mucus secretion, and late-phase inflammatory reactions), histamine is capable of mediating the first three through its H1 receptor. In the nose, mucus secretion can be reflexively mediated by H1 and possibly also by H2 receptors. In the skin the cardinal features of urticaria (vasodilation, vascular permeability, and pruritus) can be mediated by stimulation of the H1 receptor. In anaphylaxis histamine H1-receptor stimulation can mediate vascular permeability, smooth muscle contraction, and tachycardia, whereas H2-receptor stimulation can mediate mucus secretion. Stimulation of both receptors can mediate vasodilation and reduce peripheral vascular resistance. Thus although histamine is only one of many mediators of allergic disease, it plays a primary role in allergic rhinitis, urticaria, anaphylaxis, and to a lesser degree, asthma.

Anaphylaxis↗
PubMed1989

Neutrophils and mast cells: characterization of cells responsive to neutrophil-derived histamine-releasing activity (HRA-N).

Supernatants from human neutrophils (polymorphonuclear leukocytes) contain a factor capable of causing temperature and calcium-dependent histamine release from rat basophil leukemia (RBL) cells, termed neutrophil-derived, histamine-releasing activity (HRA-N). HRA-N caused dose-related histamine release from human basophils (5% to 22% net) and from isolated human cutaneous mast cells (3% to 28% net). Equivalent amounts of histamine were released from human basophils, RBL cells, and cultured mouse P cells exposed to HRA-N (16.3 +/- 3.4%, 12.2 +/- 1.2%, and 15.5 +/- 2.5%, respectively; p was not significant). Intradermal injections of HRA-N also caused chlorpheniramine-inhibitable blueing in vivo in rat and guinea pig skin. In general, supernatants that were active on RBL cells also induced histamine release from human basophils, although the magnitude of response to individual HRA-N preparation varied among basophil donors. HRA-N is stable to boiling and filters at a molecular weight greater than 1000 daltons. Boiling enhances HRA-N, suggesting the presence of a heat-labile inhibitor of HRA-N. These data suggest that HRA-N is a heat-stable factor that causes histamine release from human basophils and human cutaneous mast cells, that HRA-N is active across species lines both in vivo and in vitro, and that HRA-N acts maximally to induce histamine release under physiologic conditions.

Animals↗
PubMed1989

Neutrophil attractant/activation protein-1 (NAP-1) causes human basophil histamine release.

Basophils from five of six human donors released histamine in response to neutrophil attractant/activation protein-1 (NAP-1). Histamine release by this protein was concentration-dependent over the range of 3 x 10(-7) M to 4 x 10(-6) M. At 4 x 10(-6) M, the mean agonist-induced release was 16 +/- 3% (SEM) of total basophil histamine. For the same basophil preparations, release by anti-IgE was 35 +/- 6%. The chemotactic protein did not cause release of histamine from basophils at 0 degrees C or in the presence of 10 mM EDTA. The time-course of histamine release was rapid; release was 43% of maximal after 30 s and maximal after 1 min of incubation. Thus, in addition to its previously characterized neutrophil chemotactic and activating properties, this protein activates human basophils.

Basophils↗
PubMed1989

Desensitization to trimethoprim sulfamethoxazole in patients with acquired immune deficiency syndrome and Pneumocystis carinii pneumonia.

In three of eight patients with the acquired immune deficiency syndrome the Pneumocystis carinii pneumonia treated with intravenous trimethoprim sulfamethoxazole, drug-related reactions occurred 9, 10, and 13 days after therapy. The symptom complex consisted of a maculopapular eruption, fever, eosinophilia, and leukopenia. Oral desensitization with graded doses of trimethoprim sulfamethoxazole was successfully achieved in two of the three patients.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Neutrophils and mast cells. Comparison of neutrophil-derived histamine-releasing activity with other histamine-releasing factors.

Human neutrophil-derived histamine-releasing activity (HRA-N) was partially purified and found to contain a heat-stable 1400 to 2300-Da fraction which caused human basophils and rat basophil leukemia cells (RBL) to degranulate. The capacity of HRA-N to activate basophils was not related to the gender or atopic status of the basophil donor, but was related to anti-IgE responsiveness. Several lines of evidence suggest that HRA-N and anti-IgE induce histamine release through distinctly different mechanisms: 1) the time course of HRA-N- and anti-IgE-induced RBL histamine release are different; 2) HRA-N causes histamine release from RBL with and without surface-bound IgE; 3) lactic acid stripping of IgE from human basophils reduces anti-IgE-induced histamine release, but has no consistent effect on HRA-N-induced histamine release; and 4) passive sensitization of lactic acid-stripped basophils with IgE restores anti-IgE-induced histamine release but not HRA-N-induced histamine release. Several histamine-releasing factors (HRF) were compared with HRA-N. Human nasal HRF (HRF-NW, crude and partially purified fractions of 15 to 30, 3.5 to 9, and less than 3.5 kDa), like HRA-N, caused equal histamine release from both native and IgE-sensitized RBL. However, only the 15- to 30-kDa fraction caused histamine release from human basophils in the doses tested. Mononuclear cell HRF (HRF-M, crude and a partially purified 25 kDa Mr fraction) and platelet HRF (HRF-P, crude preparation) failed to cause histamine release from either native or IgE-sensitized RBL but caused 30 +/- 5.5% and 20 +/- 10% net histamine release from human basophils, respectively. HRA-N and HRF-NW were both stable to boiling. These data, taken together, suggest that the capacity of HRA-N to induce RBL and human basophil histamine release and of HRF-NW to stimulate RBL histamine release is independent of IgE. The data further suggest that HRA-N and HRF-NW can be distinguished by size, and that they both differ from mononuclear cell HRF and platelet HRF. Thus, it appears that inflammatory cells generate a family of distinct HRF.

Animals↗
PubMed1987

Neutrophils and mast cells. I. Human neutrophil-derived histamine-releasing activity.

Histamine release occurs during the late phase allergic reaction concomitantly with neutrophil (PMN) infiltration. To determine whether PMN might release a factor capable of causing histamine release, supernatants generated by incubating human PMN in the presence or absence of specific activators were added to rat basophilic leukemia cells (RBL) and histamine release was measured. PMN supernatants from 17 of 21 donors induced noncytotoxic histamine release. Neutrophil-derived histamine-releasing activity, termed HRA-N, was dose-dependent and supernatants from greater than or equal to 10(7) PMN/ml caused 6 to 27% net histamine release from RBL. PMN supernatants induced histamine release as effectively as did intact PMN cocultured with RBL. The capacity of various donors to generate HRA-N was not related to atopic status or gender but was inversely related to the proportion of eosinophils (EOS) contaminating the PMN isolate (the larger the proportion of EOS, the lower the histamine release). Addition of EOS to PMN during the generation of HRA-N completely inhibited histamine-releasing activity. HRA-N was not released from mononuclear cells or platelets contaminating the PMN preparation. HRA-N release was not increased by the presence of either serum-treated zymosan or phorbol myristate acetate, agents that caused dose-related release of PMN granule enzymes. Indeed, HRA-N was released from unstimulated PMN in the complete absence of granule enzyme release. HRA-N release was detectable by 15 min and the majority of release occurred between 45 and 60 min of incubation. Thus, the data indicate that HRA-N is released spontaneously from human PMN and that HRA-N release is independent of primary or secondary PMN granule release. It is attractive to suggest that release of HRA-N by PMN might act to recruit mast cells or basophils into participating in acute inflammatory reactions.

Animals↗