Biomedical subjects

D Proud

Publications and source records attributed to D Proud.

At least 73 records · Page 4Linked to original sources

PubMed1994

Soluble intracellular adhesion molecule 1 in bronchoalveolar lavage fluid of allergic subjects following segmental antigen challenge.

This study was undertaken to determine the relationship of soluble intercellular adhesion molecule 1 (sICAM-1) levels in bronchoalveolar lavage (BAL) fluid during allergic airway inflammation to those in the vascular compartment and to cellular components in the BAL fluids. A group of 11 allergic subjects underwent initial bronchoscopy during which a control BAL was performed and normal saline (NS) and specific antigen (Ag) were administered to two sublobar segments. A second bronchoscopy was performed 17 to 21 h later, and the NS and Ag segments were lavaged. Blood was drawn before each bronchoscopic procedure. The mean concentration of sICAM-1 in BAL fluid from NS-challenged segments was 59.2 +/- 7.6 ng/ml and was not different from that in unchallenged segments (51.5 +/- 5.6 ng/ml). In BAL fluid from Ag-challenged segments, mean concentrations of sICAM-1 increased significantly to 97.5 +/- 12.5 ng/ml. Segmental antigen challenge was associated with a small but statistically significant increase in sICAM-1 concentrations in serum. The concentrations of sICAM-1 in BAL fluid after antigen challenge exceeded levels that could be accounted for by passive transudation from the circulation, based upon the magnitude of increases in BAL albumin concentrations. The levels of sICAM-1 in BAL from Ag-challenged segments were correlated significantly with the total white cell, lymphocyte, neutrophil, and eosinophil counts in BAL fluids. These results are supportive of the notion that the local release of sICAM-1 may play a role in allergen-induced inflammatory processes in the airways.

Adult↗

PubMed1994

Characterization of GTP-binding proteins coupled to inhibition of adenylyl cyclase in guinea pig tracheal epithelial cells.

Many important airway epithelial cell functions are regulated by intracellular cAMP. Adenylyl cyclase, the enzyme that synthesizes cAMP, is under dual regulation in many cells, but muscarinic agonists have not been shown to inhibit adenylyl cyclase in human and dog epithelial cells, despite the presence of muscarinic receptors. We question whether the lack of inhibition was related to the absence of a component of the inhibitory pathway or a lack of coupling between the components. The GTP-binding regulatory proteins (G proteins) that regulate adenylyl cyclase activity in airway epithelium have not been well characterized. We used primary cultures of guinea pig tracheal epithelial cells as a model system and identified the G proteins that modulate adenylyl cyclase activity. Immunoblot analysis demonstrated the presence of alpha subunits corresponding to stimulatory (Gs alpha) and inhibitory [Gi alpha (2) and Gi alpha (3)] G proteins as well as beta chains. These G proteins were functionally coupled to stimulation and inhibition of adenylyl cyclase in epithelial membrane preparations. Pertussis toxin-catalyzed [32P]ADP-ribosylation of Gi alpha was significantly reduced by 100 microM GTP gamma S (78.4 +/- 3.6% of control), by 100 mM NaF (41.9 +/- 9.1% of control), and by carbachol (100 microM) (29.2 +/- 9.0% of control). Atropine (10 microM) inhibited the carbachol effect by greater than 90%, suggesting that the muscarinic receptors were functionally coupled to Gi proteins. beta-Adrenergic agonists increased adenylyl cyclase activity, but muscarinic agonists failed to inhibit this enzyme. In summary, guinea pig tracheal epithelial membranes contain muscarinic receptors, Gi alpha (2) and adenylyl cyclase, which are appropriately coupled.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate Ribose↗

PubMed1994

Glucocorticoids do not alter peptidase expression on a human bronchial epithelial cell line.

Respiratory epithelial cell surface neutral endopeptidase 24.11 (NEP-24.11) degrades proinflammatory peptides, and it has been suggested that glucocorticoids may reduce airway inflammation, in part, by upregulation of NEP-24.11. Despite the potential importance of the epithelium as a metabolic barrier, little is known regarding what other peptidases may be present on the epithelial cell surface. Using an immortalized bronchial epithelial cell line (BEAS-2B), we have shown that human epithelial cells express no detectable angiotensin-converting enzyme, carboxypeptidase N, or dipeptidyl(amino)peptidase IV, but express significant levels of aminopeptidase M (AmM), as well as NEP-24.11. The presence of these enzymes was demonstrated via their degradation of biologically active peptides and by flow cytometry. Exposure of cells to the glucocorticoid budesonide (10(-7) M) for up to 5 days did not markedly alter the expression of NEP-24.11 or AmM, as assessed by flow cytometry, nor did glucocorticoid treatment modify rates of peptide hydrolysis by NEP-24.11 or AmM. Thus, BEAS-2B cells have both AmM and NEP-24.11 on their surface, and expression of these enzymes is not altered by glucocorticoids.

Aminopeptidases↗

PubMed1994

Kinins in the pathogenesis of human airway diseases.

1. Over the past decade, data have been obtained showing that the potent vasoactive peptides known as kinins are generated in airway secretions during a variety of inflammatory airway diseases, such as allergic rhinitis, viral rhinitis and asthma. Kinin generation involves release of tissue kallikrein from airway glands, as well as increased vascular permeability and activation of the plasma kallikrein system. The activity of generated kinins is regulated by a number of cell-associated, as well as plasma-derived, peptidases. 2. Kinins can induce relevant symptoms when applied to the surface of human airways. Moreover, the effects of kinins are more pronounced in the setting of chronic inflammation. In the upper airways, kinins can stimulate glandular secretion, increase vascular permeability and stimulate sensory nerves to produce symptoms of nasal obstruction, rhinorrhea, and nasal and throat irritation. In the lower airways of asthmatics, kinins are potent inducers of edema and cause bronchoconstriction by a mechanism that involves, at least in part, neural reflexes. 3. Definitive proof of a role for kinins in human airway diseases has been difficult to obtain because receptor antagonists that have been available to date have suffered from problems of potency or duration of action. Studies are continuing, however, to understand the mechanisms by which kinins exert their effects and to delineate their importance in airway diseases.

Asthma↗

PubMed1993

A sensitive colorimetric assay for the release of tryptase from human lung mast cells in vitro.

Studies of human lung mast cells have usually focused on histamine release, although the enzymes stored in the granules may also contribute to the pathophysiology of the allergic response. We have used a simple colorimetric assay for tryptase to follow the release of proteolytic enzymes from human lung mast cells in vitro. Either human lung mast cell supernatants or authentic mast cell tryptase were mixed with benzoyl-DL-arginine-p-nitroaniline and incubated for up to 72 h at 37 degrees C. The appearance of nitroaniline was then measured at 410 nm in an ELISA plate reader. Cells were sonicated in H2O to measure total tryptase and histamine. Human lung mast cells contained the equivalent of 11.2 +/- 0.7 pg tryptase per cell and 3.2 +/- 0.3 pg of histamine. The amount of tryptase measured colorimetrically correlated with the level of tryptase measured by radioimmunoassay (Pharmacia), r = 0.92, P < 0.01. The inhibition profile of the proteolytic enzyme measured by the cleavage of BAPNA, was found to be identical to that of authentic lung mast cell tryptase. Over 90% of the maximum tryptase release was complete within 15 min whilst histamine release occurred within 5 min. In cells stimulated with 10 micrograms/ml anti-IgE we found a strong correlation between the release of tryptase and histamine, r = 0.95, P < 0.005. Finally, investigations with various pharmacological agents have supported our initial hypothesis that tryptase would mimic histamine release and provide an alternative marker for mast cell activation. In summary, we have utilised a simple enzymic assay as an indicator of human lung mast cell degranulation. In washed lung mast cells this assay appears be specific for granule tryptase and release of this activity into the supernatants of challenged cells correlates well with the presence of histamine. This assay offers several advantages over current methods of measuring mediator release from human lung mast cells in vitro and should provide an inexpensive and sensitive technique for following mast cell degranulation.

Benzoquinones↗

PubMed1993

Localization of immunoreactive tissue kallikrein in human trachea.

Tissue kallikrein is the major kininogenase detected in bronchoalveolar lavage fluids from asthmatics and may play a particularly important role in kinin generation during asthma. The present study was undertaken to determine the source of tissue kallikrein in the human lower airways. Specific antisera to human tissue kallikrein were used to localize this enzyme by immunocytochemistry in human trachea. Immunoreactive tissue kallikrein was localized in submucosal glands of the lamina propria but was not detected in epithelial cells or goblet cells. Specific staining for tissue kallikrein was not detected in all cells of the submucosal glands but was restricted to cells forming demilunes in the distal portions of the glands. When consecutive serial sections of submucosal glands were alternately stained using antiserum to tissue kallikrein and a periodic acid Schiff stain (to detect mucus), it was revealed that immunoreactive tissue kallikrein was present only in serous cells and not in mucus cells. The localization of tissue kallikrein to the serous cells of submucosal glands should facilitate studies to regulate the release of this enzyme. Regulation of tissue kallikrein release may provide a mechanism to reduce kinin generation during asthma.

Epithelial Cells↗

PubMed1993

Bradykinin effects in guinea pig tracheal epithelial cells are mediated through a B2 kinin receptor and can be inhibited by the selective antagonist Hoe 140.

Attempts to evaluate the role of kinins in airway inflammation in humans using the bradykinin receptor antagonist [DArg0-Hyp3-DPhe7]-bradykinin (NPC 567) were unsuccessful, possibly because of the low potency and poor stability of this compound. Recently, [DArg0-Hyp3-Thi5-DTic7-Oic8]-bradykinin (Hoe 140), a novel antagonist that seems to overcome these weaknesses, has been developed. The present study was performed to compare the potency and efficacy of Hoe 140 to those of NPC 567 and another antagonist, [DArg0-Hyp3-DPhe7-Ile8]-bradykinin (B7418), on kinin receptors on guinea pig tracheal epithelial cells. Radioligand binding studies showed the presence of two types of B2 kinin receptors on guinea pig tracheal epithelial cells: a high-affinity site with a Kd of 0.44 nM and Bmax of 12.1 fmol/10(6) cells (4000 sites/cell), and a lower affinity site with a Kd of 10 nM and Bmax of 16 fmol/10(6) cells (9600 sites/cell). Bradykinin-induced prostaglandin E2 production seemed to be associated primarily with the lower affinity site. All three B2 receptor antagonists displaced labeled bradykinin from both classes of binding sites and inhibited bradykinin-induced prostaglandin E2 production, but Hoe 140 was up to 40-fold more potent than NPC 567 and showed an affinity comparable to that of bradykinin for both binding sites. This higher potency of Hoe 140, and its stability against peptidases, suggests that this compound will be useful in evaluating the role of bradykinin in inflammatory diseases of the airways.

Animals↗

PubMed1992

Tryptase and histamine as markers to evaluate mast cell activation during the responses to nasal challenge with allergen, cold, dry air, and hyperosmolar solutions.

We have used assays for histamine and for the specific mast cell enzyme, tryptase, to examine the response of the nasal mucosa to provocation with several different stimuli and to evaluate the reliability of histamine as a marker of mast cell activation. High levels of histamine detected in baseline lavages of some subjects are not associated with any detectable tryptase, suggesting they are not mast cell derived. During pronounced immediate allergic responses, however, mast cell degranulation clearly occurs, and a striking correlation between histamine and tryptase is observed. This correlation is weaker when a more modest allergic response is induced, possibly reflecting differential diffusion of the two mediators across the epithelium. Provocation of susceptible individuals with cold, dry air leads to increased recoveries of both histamine and tryptase, confirming that mast cell degranulation occurs during this reaction. Although hyperosmolarity of the nasal mucosa may contribute to mast cell degranulation induced by cold, dry air, a brief exposure of the nasal cavity to hyperosmolar mannitol was not associated with measurable production of tryptase. The combined use of histamine and tryptase measurements can therefore provide useful evidence regarding the role of mast cell activation in the pathogenesis of inflammatory responses.

Adult↗

PubMed1992

Intranasal beclomethasone inhibits antigen-induced nasal hyperresponsiveness to histamine.

To determine whether intranasal steroid treatment inhibits the increased sensitivity to histamine that occurs 24 hours after nasal antigen challenge, 12 allergic volunteers were entered into a double-blind study comparing placebo or 164 micrograms of beclomethasone dipropionate twice a day for 7 days. Beclomethasone dipropionate partially reduced the early mediator response to antigen and the influx of eosinophils 24 hours later. Comparing the initial histamine challenge with that done 24 hours after antigen with the subjects on placebo, there was a significant increase in sneezes, TAME-esterase activity, and albumin. Pretreatment with intranasal beclomethasone dipropionate resulted in a reduced response to histamine 24 hours after antigen challenge. A positive correlation occurred between the number of eosinophils in the lavage before histamine challenge and the level of TAME-esterase activity (rs = 0.67, p = 0.03) during the histamine challenge that followed antigen with the subjects on placebo. We thus confirmed the increase in nonspecific nasal airway responsiveness 24 hours after antigen challenge, with a concomitant increase in eosinophils, and demonstrate its inhibition by pretreatment with intranasal steroids.

Administration, Intranasal↗

PubMed1992

The nasal response to histamine challenge: effect of the pollen season and immunotherapy.

To evaluate changes in the nasal response to histamine, we challenged 19 subjects with allergic rhinitis caused by ragweed (RW) before, during, and after the RW season with increasing doses of histamine diphosphate. We compared their response, as measured by symptoms and the levels of TAME-esterase activity and albumin recovered in the nasal lavage fluid, with response of two groups with allergic rhinitis undergoing immunotherapy with moderate-dose (N = 16) and high-dose (N = 11) RW (2 and 24 micrograms of antigen E [Amb a I] as maintenance dose, respectively). Four challenges with histamine were performed in each group: before, at the peak of, near the end of, and 2 weeks after the RW season. The three groups of subjects had similar skin sensitivity to antigen and levels of TAME-esterase activity and albumin recovered from nasal lavages after histamine challenge performed before seasonal exposure. Symptom diaries obtained throughout the season revealed a significant reduction only in the high-dose immunotherapy-treated group. At the peak of the season, the untreated group had more symptoms in response to the challenge compared with the challenges before and after the season (p = 0.04 for both groups). The saline challenge occurring before challenging with histamine also demonstrated a significant increase at the peak of the season compared with increases before the season (p = 0.02). This observation was also true for the levels of albumin and TAME-esterase activity. If the response after saline challenge was subtracted from each response after histamine challenge, no difference was found in the results between any of the visits.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

The effect of azelastine on the early allergic response.

To study the effect of azelastine on the immediate reaction to nasal allergen challenge, we performed a double blind, placebo-controlled cross-over clinical trial. Thirteen subjects with seasonal allergic rhinitis underwent nasal challenge with antigen 4 hr after a single oral 2 mg dose of azelastine. The response was monitored by counting the number of sneezes and by measuring the levels of histamine, prostaglandin D2, immunoreactive sulphidopeptide leukotrienes, kinis and TAME-esterase activity in recovered nasal lavages. After a single dose of azelastine, there was a significant reduction in sneezing (10 vs 2, P = 0.01) and in the median levels of recovered TAME-esterase activity (63.1 vs 17.5 c.p.m. x 10(-3), P = 0.01), immunoreactive sulphidopeptide leukotrienes (7.5 vs 2.1 ng/ml, P = 0.03) and kinins (1370 vs 251 pg/ml, P = 0.03), with no significant reduction in the median levels of histamine (3.7 vs 1.2 ng/ml, P = 0.2) and prostaglandin D2 (70 vs 70 pg/ml, P = 0.2) compared to placebo (numbers represent total increase over diluent challenge). These results suggest that azelastine does not inhibit mast cell activation but affects the consequences of released histamine, namely sneezing, increased vascular permeability and the generation of kinins. The results further suggest that other cells, in addition to mast cells, might be responsible for the generation of leukotrienes during the early allergic response, and that azelastine reduces their ability to generate this mediator or that inhibition of leukotriene release from mast cells occurs at lower drug concentrations.

Adult↗

PubMed1992

Platelet activation in the lung after antigen challenge in a model of allergic asthma.

The purpose of this study was to investigate whether platelets are activated and release their products in the human lung after antigen challenge. Using subsegmental antigen challenge as a model of asthma, bronchoalveolar lavage fluids from ragweed-allergic asthmatic subjects were assayed for the alpha granule products, platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG), prior to challenge (baseline) and at 5 min and 19 h after challenge with ragweed antigen. Airway segments challenged with normal saline were used as controls. Five minutes after antigen challenge, levels of platelet products in BAL fluid were not elevated from baseline or normal saline control levels. However, 19 h after antigen challenge, a 10-fold increase in platelet products in BAL fluids was found. The mean PF4 levels increased from baseline and saline control values of less than 1.0 to 7.2 ng/ml (p less than 0.05) 19 h after antigen challenge. beta-TG increased from baseline and control levels of less than 1.0 to 6.6 ng/ml (p less than 0.05). Elevations in PF4 and beta-TG were highly correlated with each other (r = 0.98, p less than 0.0001). Levels of platelet products during the 19-h response correlated with albumin, with kinins, with the prostaglandins 6-keto-PGF1 alpha, PGE2, and PGF2 alpha, and with the eosinophil-derived proteins, eosinophil-derived neurotoxin and eosinophil peroxidase. We conclude that platelet activation in the lung is a feature of the late inflammatory response to antigen challenge and that platelets may play an important role in allergic inflammation and asthma.

Adult↗

PubMed1992

Elevation of tissue kallikrein and kinin in the airways of asthmatic subjects after endobronchial allergen challenge.

Bronchial tissue kallikrein is the major kininogenase activity in the airways of asthmatic subjects. The relationship of IgE-mediated events to its release and/or activation is unknown, however, and is the subject of this report. Seven subjects with mild atopic asthma underwent endobronchial challenge with relevant aeroallergen. Baseline pre-allergen lavage and sequential post-challenge lavages were collected over an approximate 10-minute time course. Individual aliquots were analyzed separately and compared with saline control lavages performed in a separate lobe. In five of the seven subjects, an increase in tissue kallikrein activity, measured by cleavage of the synthetic substrate Val-Leu-Arg-pNA, was identified in the post-challenge lavages. The antigenic identity of the enzymatic activity was confirmed as a tissue kallikrein in each case by immunoblotting. Tissue kallikrein activity was highly correlated with the appearance of immunoreactive histamine and kinin (p = 0.0001). High molecular weight kininogen influx and cleavage was detected in the post-challenge samples by immunoblotting and paralleled the detection of kinin in BAL fluid. Two of the subjects, despite clinical profiles similar to those of the five positive responders, failed to react to endobronchial challenge. Saline control lavages contained detectable kallikrein, kinin, and histamine in two subjects; in each case, however, this was significantly less than in the post-allergen samples. The results demonstrate a close association between immediate type hypersensitivity events in the lower airway and the appearance of active kallikrein, kininogen substrate, and the liberation of kinin.

Adult↗

PubMed1992

Local application of atropine attenuates the upper airway reaction to cold, dry air.

In some individuals, inhalation of cold, dry air (CDA) provokes symptoms of rhinitis, accompanied by an increase in the levels of inflammatory mediators and markers of plasma leakage of recovered nasal lavages. Because rhinorrhea is a major component of this reaction and because nasal glands are heavily innervated by the parasympathetic system, we assessed the effect of atropine on the nasal reaction to CDA. Using a double-blind, randomized, crossover design, we administered a total dose of 0.5 mg of atropine or placebo intranasally to 18 volunteers before provocation with CDA. The reaction was monitored with symptom scores and by measuring the concentrations of histamine, N-alpha-p-tosyl-L-arginine methyl ester (TAME)-esterase activity and albumin, as well as the osmolality of lavage fluids before and after the provocation. Atropine significantly reduced rhinorrhea, the levels of histamine, and TAME-esterase activity as well as the osmolality of recovered lavage fluids, but had no effect on nasal congestion or albumin. Even with atropine, however, rhinorrhea and TAME-esterase activity were still significantly increased over the prechallenge baseline. Our results demonstrate that atropine-sensitive parasympathetic efferent pathways contribute to the CDA-induced rhinitis. We speculate that (1) the glandular and the vascular events of the upper airway reaction to dry air have different pathophysiologic mechanisms; (2) a significant component of TAME-esterase activity in lavage fluids may be of glandular origin; and (3) in addition to parasympathetic nerve activation, other mechanisms are involved in the upper airway reaction to dry air. The mechanism(s) leading to the reduction of histamine is unknown.

Administration, Intranasal↗

PubMed1992

Cultured human synovial fibroblasts rapidly metabolize kinins and neuropeptides.

Kinins and substance P have been implicated in the pathogenesis of inflammatory arthritis by virtue of their abilities to induce vasodilation, edema, and pain. The relative biological potencies of these peptides in vivo would depend at least in part upon their rates of catabolism in the joint. We hypothesized that human synovial lining cells may regulate intraarticular levels of kinins and neuropeptides via degradation by cell surface-associated peptidases. We exposed intact human synovial fibroblasts to kinins and substance P, in the presence or absence of specific peptidase inhibitors, and measured the amount of intact substrate remaining and degradation product(s) generated over time. Aminopeptidase M (AmM; EC 3.4.11.2), neutral endopeptidase-24.11 (NEP-24.11; EC 3.4.24.11), and dipeptidyl(amino)peptidase IV (DAP IV; EC 3.4.14.5) were identified on the cell surface of synovial cells. Bradykinin degradation was due entirely to NEP-24.11 (1.39 +/- 0.29 nmol/min per well). Lysylbradykinin was also degraded by NEP-24.11 (0.80 +/- 0.19 nmol/min per well); however, in the presence of phosphoramidon, AmM-mediated conversion to bradykinin (3.74 +/- 0.46 nmol/min per well) could be demonstrated. The combined actions of NEP-24.11 (0.93 +/- 0.15 nmol/min per well) and DAP IV (0.84 +/- 0.18 nmol/min per well) were responsible for the degradation of substance P. AmM (2.44 +/- 0.33 nmol/min per well) and NEP-24.11 (1.30 +/- 0.45 nmol/min per well) were responsible for the degradation of the opioid peptide, [Leu5]enkephalin. The identity of each of the three peptidases was confirmed via synthetic substrate hydrolysis, inhibition profile, and immunological identification. The profiles of peptidase enzymes identified in cells derived from rheumatoid and osteoarthritic joints were identical. These data demonstrate the human synovial fibroblast to be a rich source of three specific peptidases and suggest that it may play a prominent role in regulating peptide levels in the joint.

Antigens, CD↗

PubMed1992

Evaluation of a bedtime dose of a combination antihistamine/analgesic/decongestant product on antigen challenge the next morning.

The effects of CAAD (diphenhydramine hydrochloride, 50 mg; pseudoephedrine hydrochloride, 60 mg; acetaminophen, 1 g in 10% ethanol) were evaluated in a double-blind, three-way, placebo-controlled, cross-over study on 18 volunteers with allergic rhinitis. The number of sneezes following nasal challenge with antigen was significantly reduced after a bed-time dose of CAAD (P less than .005) and a single dose of diphenhydramine (P less than .001) given 2 hours before the challenge. The levels of N-alpha-tosyl-L-arginine methyl ester (TAME) activity decreased after diphenhydramine treatment, while histamine levels following challenge were not different. The drowsiness reported after CAAD was equal to placebo, but significantly less than diphenhydramine (P less than .002 for both). The active treatments reduced the actions of histamine without suppressing its release from mast cells. The effect of CAAD persists 10 hours after administration without inducing drowsiness.

Acetaminophen↗

PubMed1992

Characterization of kinin receptors on human synovial cells and upregulation of receptor number by interleukin-1.

Bradykinin has been implicated in the pathogenesis of inflammatory arthritis by virtue of its potent proinflammatory properties. We have previously shown bradykinin to be a potent stimulus for the release of prostanoids from interleukin-1 (IL-1)-treated, but not untreated, human synovial cells. We hypothesize that one mechanism by which IL-1 induces responsiveness to bradykinin is by upregulation of number or affinity of kinin receptors on human synovial cells. We performed [3H]bradykinin binding studies in intact human synovial tissue and in cultured human synovial cells. Specific, saturable [3H]bradykinin binding sites in intact synovia were identified by autoradiographic localization and were present in much higher density in rheumatoid, than in osteoarthritis, synovia. In untreated human synovial cells in culture, a single (B2) class of kinin binding sites with a Kd of 2.3 nM and Bmax of 58 +/- 9 fmol/10(6) cells was demonstrated. In matched experiments, IL-1 treatment enhanced specific [3H]bradykinin binding 1.5- to 2.0-fold above that observed in untreated cells. This enhancement was attributable to an increase in Bmax (53 +/- 4 vs. 105 +/- 24 fmol/10(6) cells in untreated and IL-1-treated cells, respectively), rather than an alteration in Kd (1.7 and 1.4 nM, respectively). The potencies of a series of kinin analogs and antagonists and unrelated peptides in displacing [3H]bradykinin from IL-1-treated cells correlated well with their abilities to induce prostanoid release. These studies provide novel information regarding the nature of kinin receptors in intact human synovia and in cultured human synovial cells, their regulation by IL-1 and their role in IL-1-treated cells in kinin-mediated prostaglandin E2 production.

Autoradiography↗

PubMed1992

Modulation of kinin responses in human synovium by interleukin-1.

Bradykinin (BK) is a weak stimulus for prostaglandin E2 (PGE2) release in untreated human synovial cells, but a potent stimulus in interleukin-1 (IL-1) pretreated cells. The mechanism(s) by which IL-1 induces responsiveness of synovial cells to BK appears to be multifactorial. IL-1 not only upregulates the number of kinin receptors on these cells, but may also upregulate a calcium-dependent process involved in the synthesis of prostaglandins.

Arthritis, Rheumatoid↗