Immediate hypersensitivity.
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Chemotactic Factors, Eosinophil↗
Biomedical subjects
M Kaliner
Publications and source records attributed to M Kaliner.
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↗
Gustatory rhinitis: a syndrome of food-induced rhinorrhea.
The consumption of certain foods causes watery rhinorrhea (gustatory rhinitis) in many individuals. To examine the underlying mechanisms responsible for this common phenomenon, 12 subjects ingested control foods and positive foods (foods that cause rhinorrhea). Nasal lavages performed 10 minutes after each food challenge were analyzed for albumin and total protein. Positive food challenge, but not control food challenge, induced rhinorrhea in all subjects. Positive food challenge increased albumin (7.8 +/- 1.9 to 24.5 +/- 7.6 mg/L; p less than 0.025) and total protein (79 +/- 9 to 258 +/- 41 mg/L; p less than 0.001) without altering the ratio of albumin to total protein (albumin percent). Nasal pretreatment with atropine clinically blocked the positive food-induced rhinorrhea and significantly inhibited secretion of both albumin and total protein, again without affecting the albumin percent. Thus, gustatory rhinitis is produced by spicy foods that stimulate atropine-inhibitable muscarinic receptors (probably on submucosal glands), and the syndrome can be treated prophylactically by use of topical atropine.
Administration, Topical↗
Blood histamine concentrations are not elevated in humans with septic shock.
Histamine has been suggested as an important mediator of the cardiovascular abnormalities during septic shock. To determine if blood histamine levels were increased during human sepsis and septic shock, plasma histamine was measured using a very sensitive radioenzyme assay employing histamine N-methyltransferase (HNMT) in the following patient groups: normal controls (n = 76), nonseptic critically ill (n = 12), nonseptic shock (n = 2), sepsis without shock (n = 28), and septic shock (n = 41). Using this enzyme binding assay, all these groups had similar, normal plasma histamine concentrations, except those patients with septic shock whose mean histamine measurements were significantly reduced (p less than .002). This decrease was found to be due to an artifact of the assay: plasma contained a circulating inhibitor that falsely lowered the measured histamine level. Fractionation of septic shock plasma using molecular exclusion membranes and gel filtration revealed a 5000 MW inhibitory factor. After removal of this inhibitor from plasma, septic shock plasma histamine levels were normal. Thus, septic shock patients may have a circulating inhibitor of the HNMT enzyme, but plasma histamine concentrations are normal. Histaminemia is unlikely to play an important role in the pathogenesis of septic shock in humans.
Chromatography, Gel↗
Substance P receptor-mediated secretion of respiratory glycoconjugate from feline airways in vitro.
The effect of substance P (SP) and other tachykinins on respiratory glycoconjugate (RGC) release was studied in a feline tracheal organ culture system. SP in concentrations of 10(-5) and 10(-6) M stimulated an increase in RGC release of 35 +/- 8% and 18.5 +/- 5%, respectively. The addition of the protease inhibitor aprotinin or the enkephalinase inhibitor thiorphan to the cultures had no effect on the baseline secretion of RGC but markedly potentiated the activity of SP. SP in the presence of aprotinin or thiorphan was active at 10(-8) -10(-9) M concentrations and was more potent at each concentration studied (in the presence of peptidase inhibitors). Among other tachykinins studied, only physalaemin in the presence of aprotinin had a clear stimulatory effect on RGC release at 10(-6) M concentration (26% +/- 5% increase above control, n = 4, p less than 0.02); kassinin, neurokinin A, and neurokinin B had little or no effect on RGC secretion in concentrations of 10(-6) M or less. Autoradiographic studies of [125I]SP binding revealed SP receptor expression in the submucosal glands of the feline trachea. [125I]SP binding was inhibited in the presence of excess unlabeled SP. We conclude that SP receptors are present in the feline tracheal submucosal glands and that binding to SP receptors results in RGC secretion.
Animals↗
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↗
IgE immunotoxins. Effect of an IgE-ricin A chain conjugate on rat skin histamine content.
Immunotoxins--toxins covalently conjugated to specific antibodies--have been studied as possible agents in the treatment of cancer. The avid binding of IgE antibodies to FcR on mast cells and basophils suggested the possible use of an IgE-immunotoxin in the treatment of malignant mastocytosis or as a method to generate mast cell-depleted animals for study. To this end, the effect of a covalent conjugate of rat myeloma IgE and ricin A chain on rat cutaneous mast cells was examined in vivo. IgE-ricin A chain was capable of binding to and sensitizing cutaneous mast cells in vivo as indicated by a bluing response to intracutaneous anti-ricin A chain. IgE-ricin A chain, given either as a single dose or, even more effectively, as two split doses, significantly reduced cutaneous histamine content for 6 to 8 days. Neither a mixture of IgE and ricin A chain that were not conjugated nor the induction of cutaneous mast cell degranulation with anti-IgE affected cutaneous histamine levels. Therefore, IgE-ricin A chain produces a prolonged depletion of cutaneous histamine levels.
Animals↗
Late-phase IgE-mediated reactions.
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Allergens↗
Urine-histamine levels in patients with hereditary angioedema (HAE).
Hereditary angioedema (HAE) is defined clinically by recurrent, self-limited episodes of angioedema. The disease is defined biochemically by a deficiency in the functional activity of C1 esterase inhibitor. To date, the actual serum or tissue mediator(s) responsible for the angioedematous lesion remains controversial. Although antihistaminics have been clearly demonstrated to have no efficacy in the long-term treatment of this disorder, instances of elevated urine-histamine levels in patients with HAE raises the possibility of a role for histamine in the pathophysiology of this disease. Urine samples were collected from 28 asymptomatic and from 11 symptomatic patients with HAE. The urine-histamine levels were compared with levels of 41 normal control subjects. With the exception of one asymptomatic patient with HAE whose diagnoses also included rheumatoid arthritis and secondary Sjögren's syndrome, the urine-histamine levels from asymptomatic patients with HAE were similar to values obtained from normal control subjects. Except for data from two patients with HAE, urine-histamine levels from symptomatic patients with HAE were also indistinguishable from levels of normal volunteers. These data suggest that the vast majority of patients with HAE have normal urine-histamine levels both during and between attacks. Consequently, histamine is unlikely to play a pathophysiologic role in HAE.
Angioedema↗
Ultrastructural changes in human skin mast cells during antigen-induced degranulation in vivo.
Human skin mast cells were degranulated in vivo by intradermal injection of antigen. Biopsy specimens of control and stimulated skin were obtained at 5 minutes, again at 10 to 15 minutes, and analyzed by electron microscopy. Degranulation, defined as dissolution of granule contents and swelling in at least 20% of secretory granules of mast cells was observed in one third of mast cells at 5 minutes and in nearly two thirds of mast cells at 10 to 15 minutes, but was absent in biopsy specimens of control subjects. Anaphylactic degranulation was characterized by extensive fusion of granules to form degranulation channels, fusion of channels with the cell membrane to form large pores, and exocytosis of amorphous or fibrillar granule matrix into the connective tissue. Extruded secretory granules of skin mast cells persist for at least 15 minutes in the connective tissues, in apparent contrast to the process of in vivo degranulation in nasal and lung mast cells.
Allergens↗
Evaluation of a radioimmunoassay for histamine measurement in biologic fluids.
A new radioimmunoassay for the measurement of histamine in biologic fluids was evaluated. Assay selectivity and specificity were achieved by "succinyl-glycinamide derivatization" of histamine in samples to mimic the immunogen used to generate the monoclonal antibody. The assay exhibits a linear response from 0.1 to 5.0 ng/ml of histamine and the monoclonal antibody used has partial recognition of only N-methylhistamine (other than histamine). With minimal modifications, the assay can accurately measure histamine in plasma, urine, and buffer. Normal ranges for human subjects were established: plasma levels are 0.193 +/- 0.08 ng/ml (n = 40) and urine levels are 20.9 +/- 11.2 micrograms histamine/gm creatinine (n = 10).
Body Fluids↗
Dexamethasone inhibits respiratory glycoconjugate secretion from feline airways in vitro by the induction of lipocortin (lipomodulin) synthesis.
The effect of glucocorticoids on respiratory glycoconjugate (RGC) secretion was studied in a cat tracheal organ culture system. Dexamethasone (10(-5) to 10(-9) M) added to culture medium for 24 h caused a dose-related reversible inhibition of RCG of as much as 40% with a peak effect at 24 to 60 h after initiation of dexamethasone treatment. A monoclonal antilipocortin antibody added to the cultures blocked the inhibitory effect of dexamethasone on RGC secretion and accelerated the reversal of the dexamethasone effect after discontinuation of dexamethasone treatment. A control antibody without antilipocortin activity had no effect on RGC secretion or dexamethasone-induced inhibition of RGC secretion. Measurement of the concentration of lipocortin in airways revealed a 220% increase after treatment with dexamethasone for 24 h. We conclude that dexamethasone inhibits RGC secretion through the induction of lipocortin synthesis.
Animals↗
Dexamethasone reduces rat tracheal goblet cell hyperplasia produced by human neutrophil products.
An experimental model leading to goblet cell hyperplasia was developed in order to examine the possible preventive effects of glucocorticosteroids. Human peripheral blood neutrophils were isolated and either freeze-thaw lysed or activated with serum opsonized zymosan. Supernatants from these neutrophil preparations were then instilled transorally into the tracheas of male Sprague-Dawley rats. After 7-35 days, the rats were sacrificed; the lower tracheas were excised, fixed in formalin, and stained with periodic acid-Schiff and alcian blue; and the goblet cells and total epithelial cells were counted. Supernatants from both lysed neutrophils and zymosan-activated neutrophils stimulated a 50% and 42% (respectively) increase in goblet cells after 3 weeks as compared to controls. Purified human neutrophil or porcine pancreatic elastase also caused goblet cell hyperplasia, while sham challenge, challenge with buffer, or challenge with lysates of human mononuclear cells failed to affect goblet cell number. The increase in goblet-cell number was maximal by three weeks and persisted through 35 days. Treatment of animals with glucocorticosteroids administered by the addition of dexamethasone to the drinking water (2 mg/l for 1 week followed by 0.2 mg/l for 2 weeks) ablated the goblet cell hyperplasia produced by neutrophil lysates or elastase alone. We conclude that goblet cell hyperplasia may be induced with insufflated neutrophil products and that this action can be inhibited by treatment with corticosteroids.
Animals↗
Rhinitis and asthma.
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Adrenergic beta-Agonists↗
Effects of sex hormones on basophil histamine release in recurrent idiopathic anaphylaxis.
A subset of patients with recurrent anaphylaxis experience ovarian hormone-related exacerbations. Symptoms in several of these women may be provoked by gonadotropins or progesterone (P) and improved by ovarian suppression, with long-term remissions noted in several patients after oophorectomy. Since adverse reactions to P might explain this association, the effects of P and estrogen on basophil histamine release from these patients were studied. Eight patients and 10 control subjects were examined. Neither estrogen nor P caused histamine release from the basophils of patients or control subjects. Moreover, anti-IgE-induced histamine release was not influenced by P or estrogen. Attempts to culture basophils for 24 hours revealed that basophil preparations from eight of 10 normal subjects but only three of eight patients retained the capacity to respond to anti-IgE after 24 hours (p = 0.088). Culture with dexamethasone reduced anti-IgE-induced histamine release in all subjects, and the possibility that P might interfere with the effect of dexamethasone was also studied. P failed to affect dexamethasone-induced reduction of basophil histamine release. Therefore, P and estradiol appear to have no effect on basophils from either patients with hormone-related exacerbations of anaphylaxis or from control subjects.
Adolescent↗
The pathogenesis of severe asthma: a consensus report from the Workshop on Pathogenesis.
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Acute Disease↗
Histamine levels in bronchoalveolar lavage from patients with asthma, sarcoidosis, and idiopathic pulmonary fibrosis.
Bronchoalveolar lavage (BAL) has been used extensively as a research tool to elucidate immunologic events occurring in the lower respiratory tract of patients with numerous diseases and, most recently, to study patients with asthma. We assessed mast-basophiloid cell numbers and histamine levels with a sensitive histamine assay, lower limit of sensitivity, 25 pg/ml, in BAL fluid from normal individuals (n = 9) and compared these results to those obtained from patients with sarcoidosis (n = 31), idiopathic pulmonary fibrosis (IPF) (n = 8), and mild asthma (n = 7). Patients with sarcoidosis demonstrated a significant increase in total BAL mast-basophiloid cells, 9.6 +/- 4.1 X 10(4), compared to total cells in normal individuals, 0.0, p = 0.03, whereas only patients with IPF had significant elevations in BAL histamine levels, 1315 +/- 737 pg/ml, versus levels in normal individuals, 161 +/- 54 pg/ml, p = 0.002. A good correlation existed between histamine levels on an aliquot of lysed BAL cells and BAL histamine levels, R = 0.655 and p = 0.02, but not with either the total number or percent mast-basophiloid cells in BAL assessed on Wright's stained cytocentrifuge preparations. Subjects with asthma had both normal numbers of BAL mast-basophiloid cells and histamine levels. These data suggest that BAL histamine levels are easily quantified, the reason(s) for elevations in BAL histamine levels in IPF need further investigation, BAL histamine levels in subjects with asthma are not elevated in those with mild and stable disease, and lumenal mast-basophiloid cells are one major source of BAL histamine.
Adult↗
IgE-immunotoxins. I. IgE-intact ricin.
An IgE immunotoxin consisting of rat IgE myeloma protein, IR 162, conjugated via the heterobifunctional linking agent N-succinimidyl-3-(2-pyridyldithio)propionate to intact ricin was synthesized and evaluated. The capacity of this IgE-immunotoxin to bind to rat basophilic leukemia cells (RBL cells) and to inhibit RBL cell incorporation of [3H]leucine was assessed. The IgE-intact ricin conjugate sensitized RBL cells for histamine release after treatment with anti-IgE with a time-course of sensitization and dose-response equivalent to native IgE. Intact ricin and IgE-intact ricin were both cytotoxic to RBL cells as assessed by [3H]leucine incorporation. Lactose (50 mM) competed with intact ricin binding and toxicity such that more than 100 ng/ml ricin (8 times its IC50 in the absence of lactose) was required for ricin to kill RBL cells in the presence of lactose. Lactose (50 mM) was not able to fully inhibit 1-100 ng/ml IgE-ricin immunotoxin killing of RBL cells. Saturation of RBL cell IgE receptors by preincubation with IgE totally inhibited IgE-intact ricin-induced toxicity, in the presence of lactose, indicating that toxicity required IgE Fc receptor binding.
Animals↗