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PubMed2006

Biochemical markers in the follow-up of medullary thyroid cancer.

Medullary thyroid cancer (MTC) shares biochemical features with other neuroendocrine tumors but the particular characteristics are largely unexplored. We investigated the biochemical neuroendocrine profile of MTC and whether specific markers could be useful in follow-up. In addition to the standard tumor marker calcitonin, plasma carcino-embryonic antigen (CEA), plasma catecholamines, (platelet) serotonin, chromogranin A, tryptase, and urinary markers of catecholamine, histamine, and serotonin metabolism were prospectively determined in 46 patients with histologically proven MTC. Patients were divided according to the stage of disease: group 1, no evidence; group 2, stable disease (SD); and group 3, progressive disease (PD). Plasma dopamine was increased in the majority of the patients with SD and PD; however it did not correlate with extent of disease. Elevated plasma platelet levels of serotonin were only present in patients with multiple endocrine neoplasia 2 with SD or PD but did not differ between those groups. Histamine metabolites were elevated in 20% of patients with SD and PD. In addition to plasma calcitonin, only CEA and chromogranin A could differentiate between stable and progressive MTC. MTCs are capable of synthesizing catecholamines, serotonin, and histamine metabolites underscoring that MTCs have metabolic characteristics in common with other neuroendocrine tumors. Thus far, clinical usefulness and relevance seems limited. The most useful markers in the follow-up of MTC are plasma calcitonin and CEA.

Adult↗
PubMed2001

Stress and immune mediators in miscarriage.

BACKGROUND: Stress is thought to be abortogenic and psycho-neuro-immunological pathways have been suggested to be involved in triggering miscarriages. From experiments in pregnant mice exposed to stress some insights into the underlying mechanisms have been gained, delineating immunological imbalances as a cause of pregnancy failure. In order to test the validity of the conclusions drawn from murine experiments and the role of stress in human pregnancy loss, the following study was performed. METHODS: We used an established perceived stress questionnaire and measured the stress score of women with a confirmed diagnosis of first trimester spontaneous abortion (n = 94). Decidual tissue was investigated by immunohistochemistry and in-situ hybridization to detect the presence and distribution of immunocompetent decidual cells [CD56(+) natural killer (NK) cells, CD8(+)and CD3(+) T cells, tryptase(+) mast cells (MCT(+)) and tumour necrosis factor (TNF)-alpha(+) cells]. The patient cohort was divided into women experiencing low or high levels of stress. RESULTS: In the decidua of women with high stress scores we observed significantly higher numbers of MCT(+), CD8(+) T cells and TNF-alpha(+) cells per mm(2) tissue (P < or = 0.05). No significant differences between individuals with lower or higher stress scores could be observed with respect to decidual CD56(+) NK and CD3(+) T cells. CONCLUSIONS: Using a questionnaire to score perceived stress in humans may be a valid approach to assess non-biased stress scores. Stress-triggered abortion in humans, identified by a questionnaire, can be linked to immunological imbalances.

Abortion, Spontaneous↗
PubMed1998

Mast cell regulation of human endometrial matrix metalloproteinases: A mechanism underlying menstruation.

Endometrial matrix metalloproteinases (MMPs), which increase dramatically at menstruation, are purported to cause the focal tissue breakdown at menstruation, but how their expression or activation is locally regulated is unknown. Mast cell activation occurs within perimenstrual endometrium, and we postulated that mast cell products would regulate endometrial MMPs. We have examined the interaction between human mast cells and endometrial stromal cells with regard to MMP production and activation. The human mast cell line (HMC-1) in coculture with stromal cells stimulated stromal cell proMMP-1 and proMMP-3, and to a lesser extent proMMP-2 production, with increasing stimulation as mast cell number increased. Mast cell-conditioned medium also increased both protein and mRNA for stromal proMMP-1 and proMMP-3, this being abrogated by preadsorption of mast cell-conditioned medium with antisera to interleukin-1 and tumor necrosis factor alpha. Mast cell-conditioned medium added to stromal cell culture medium in vitro along with added heparin (which stabilizes tryptase activity) resulted in the appearance of molecular weight forms indicative of active MMP-3 and MMP-1. Thus activated mast cells within the endometrium prior to menstruation have the potential to stimulate MMP production by endometrial stromal cells and to initiate precursor activation, and are likely to account for the local nature of endometrial MMP action resulting in foci of tissue breakdown at menstruation.

Animals↗
PubMed2002

Mast cells with bilobed or multilobed nuclei in a nodular lesion of a patient with urticaria pigmentosa.

Mast cells with bilobed or multilobed nuclei have only rarely been observed in the bone marrow of patients with systemic mastocytosis and in a case of subdural mast cell sarcoma. To our knowledge, they have not been reported in cutaneous mast cell disease. We report a rare occurrence of mast cells with bilobed or multilobed nuclei (atypical mast cell type II) in a nodular lesion of a 24-year-old woman with urticaria pigmentosa. The typical and atypical mast cells were confirmed by Giemsa and Leder's naphthol-AS-D-chloroacetate esterase stains and by immunohistochemical staining for tryptase and KIT protein (CD117). Although the nodular lesion with atypical mast cells did not appear to be cytologically malignant, the occurrence of atypical mast cells in a nodular lesion but not in a papular lesion might denote progression of the disease as suggested by the emergence of cells positive for p53.

Adult↗
PubMed1998

Fatal anaphylaxis due to fire ant stings.

Imported fire ants (Solenopsis invicta and Solenopsis richteri) are the source of a potentially lethal environmental hazard in the southeastern United States. Because of their resistance to natural and chemical control, fire ants can overwhelm their environment, causing destruction of land and animals. Fire ants can also cause a variety of health problems in humans, ranging from simple stings to anaphylaxis and death. We present a case of a 30-year-old woman who died of anaphylaxis following multiple fire ant stings. At autopsy, multiple skin lesions characteristic of those produced by fire ant stings were present on her arm. Postmortem blood samples were positive for imported fire ant venom-specific IgE antibodies (5654 ng/ml) and tryptase (12 ng/ml). Deaths caused by imported fire ant stings are rare but are likely to become more common as the fire ant population expands. In this report, we review deaths due to fire ant stings, discuss postmortem laboratory findings, and stress the importance of recognizing the characteristic skin lesions produced by fire ants.

Adult↗
PubMed2003

Morphologic and immunophenotypic properties of neoplastic cells in a case of mast cell sarcoma.

Mast cell sarcoma is an extremely rare and aggressive type of mast cell disease. Only a few cases have been described so far, and little is known about the biology and phenotype of afflicted cells. We describe morphologic and immunophenotypic properties of neoplastic mast cells in a case of an intracranial mast cell sarcoma. In Wright-Giemsa-stained cytospin preparations, the morphology of dispersed cells appeared to be highly atypical with a considerable percentage of metachromatic blasts and mast cells with bilobed or multilobed nuclei. Combined toluidine blue/immunofluorescence staining revealed expression of CD13, CD45, CD88, CD116, and CD117 (c-KIT) on neoplastic mast cells. As assessed by immunohistochemistry, mast cells were immunoreactive for tryptase and CD68R, In contrast, the CD2 antigen that is expressed in mast cells in patients with indolent systemic mastocytosis was not detectable. Mast cells also failed to display the c-KIT mutation Asp-816-Val, which is typically found in systemic mast cell disorders. Together, neoplastic mast cells in a case of mast cell sarcoma were found to exhibit unique morphologic, phenotypical, and molecular features when compared with mast cells in indolent mastocytosis or normal tissue mast cells.

Antigens, CD↗
PubMed2003

Anaphylactic and anaphylactoid reactions occurring during anesthesia in France in 1999-2000.

BACKGROUND: Anaphylactic and anaphylactoid reactions occurring during anesthesia remain a major cause of concern for anesthesiologists. The authors report the results of a 2-yr survey of such reactions observed during anesthesia in France. METHODS: Between January 1, 1999, and December 31, 2000, 789 patients who experienced immune-mediated (anaphylaxis) or nonimmune-mediated (anaphylactoid) reactions were referred to one of the 40 participating centers. Anaphylaxis was diagnosed on the basis of clinical history, skin tests, and/or specific immunoglobulin E assay. RESULTS: Anaphylactic and anaphylactoid reactions were diagnosed in 518 cases (66%) and 271 cases (34%), respectively. The most common causes of anaphylaxis were neuromuscular blocking agents (NMBAs) (n = 306, 58.2%), latex (n = 88, 16.7%), and antibiotics (n = 79, 15.1%). Rocuronium (n = 132, 43.1%) and succinylcholine (n = 69, 22.6%) were the most frequently incriminated NMBAs. Cross-reactivity between NMBAs was observed in 75.1% of cases of anaphylaxis to an NMBA. No difference was observed between anaphylactoid and anaphylactic reactions when the incidences of atopy, asthma, or drug intolerance were compared. However, atopy, asthma, and food allergy were significantly more frequent in the case of latex allergy when compared with NMBA allergy. Clinical manifestations were more severe in anaphylaxis. The positive predictive value of tryptase for the diagnosis of anaphylaxis was 92.6%; the negative predictive value was 54.3%. The diagnostic value of specific NMBA immunoglobulin E assays was confirmed. CONCLUSIONS: These results further corroborate the need for systematic screening in the case of anaphylactoid reaction during anesthesia and for the constitution of allergoanesthesia centers to provide expert advice to anesthesiologists and allergists.

Adult↗
PubMed2005

Anaphylaxis during anesthesia in Norway: a 6-year single-center follow-up study.

BACKGROUND: Several studies have recognized neuromuscular blocking agents as the most common cause of anaphylaxis during general anesthesia, but the reported frequencies vary considerably between countries. In Norway, the issue has raised special concern because of reports from the Norwegian Medicines Agency that suggest a high prevalence. This article presents the results from a standardized allergy follow-up examination of 83 anaphylactic reactions related to general anesthesia performed at one allergy center in Bergen, Norway. METHODS: Eighty-three cases were examined during the 6-yr period of 1996-2001. The diagnostic protocol consisted of case history, serum tryptase measurements, specific immunoassays, and skin tests. RESULTS: Immunoglobulin E-mediated anaphylaxis was established in 71.1% of the cases, and neuromuscular blocking agents were by far the most frequent allergen (93.2%). Suxamethonium was the most frequently involved substance, followed by rocuronium and vecuronium. The few reactions in which other allergies could be detected were mainly linked to latex (3.6%). CONCLUSIONS: Neuromuscular blocking agents were the dominating antigens causing immunoglobulin E-mediated anaphylaxis in this study. The data could not be used for estimation of the incidence of allergy toward neuromuscular blocking agents in Norway. Larger patient samples, standardization of reporting, and diagnostic protocols should be pursued by network formation to produce data more suitable for epidemiologic research.

Adult↗
PubMed1998

Mast cells in smooth muscle tumors of the uterus.

Mast cells (MCs) have been reported in the myometrium and uterine smooth muscle tumors. We examined the number of MCs in various uterine smooth muscle tumors (including leiomyosarcomas) and assessed whether this feature might be of value in their pathologic diagnosis. The number of MCs in 95 uterine smooth muscle tumors, including 55 ordinary leiomyomas, 17 cellular leiomyomas, 8 bizarre leiomyomas, and 15 leiomyosarcomas, was counted using toluidine blue and immunohistochemical staining. The number of MCs that stained for tryptase was lowest in leiomyosarcoma and next lowest in ordinary leiomyoma; the number in each of these two groups was significantly lower than in the myometrium (p < 0.001). In cellular and bizarre leiomyomas, the number of MCs was significantly higher than in ordinary leiomyoma (p < 0.001 and p < 0.001, respectively) and leiomyosarcoma (p < 0.001 and p < 0.005, respectively). Statistical analysis revealed that counting the number of MCs and using a cut-off value of 16 MCs per high-power-field is useful for the differential diagnosis of leiomyosarcomas from cellular leiomyoma and bizarre leiomyoma, yielding 100% sensitivity and 96% specificity. The number of MCs was significantly lower in leiomyosarcomas at TNM stages III and IV than in those at stages I and II (p < 0.05), but there was no significant correlation between the number of MCs and patient survival. These results suggest that the number of MCs might be useful as part of a multivariate approach to the differential diagnosis of leiomyosarcoma from bizarre or cellular leiomyoma.

Cell Count↗
PubMed1995

Effects of iopromide on vasoactive peptides and allergy-mediated substances in healthy volunteers.

RATIONALE AND OBJECTIVES: Little information is available about the direct action of angiographic contrast media on vasoactive peptides and allergy-mediated substances in humans. This study defined the acute effects of iopromide, a nonionic contrast medium (370 mg/mL iodine), on vasoactive peptides, allergy-mediated substances, and hemodynamic parameters in healthy volunteers. METHODS: Pulmonary digital subtraction angiography was performed in seven healthy volunteers with no cardiovascular or pulmonary disease. Iopromide was administered as a total volume of 100 mL through a 7-Fr catheter inserted in the right femoral vein. The injected volumes and duration of injection (15-20 mL/second) were kept constant. The following hemodynamic parameters were monitored continuously: results of electrocardiogram, heart rate, and phasic and mean pulmonary arterial and peripheral arterial pressures. Blood samples were obtained before and 3 to 5 minutes after injection of contrast media to determine the concentrations of the following vasoactive peptides: renin, angiotensin I-converting enzyme, angiotensin II, aldosterone, atrial natriuretic peptide, antidiuretic hormone, cyclic guanosine monophosphate, and myoglobin; and to allergy-mediated substances such as tryptase, eosinophil protein X, and eosinophil cationic protein, using radioimmunoassay techniques. RESULTS: Iopromide substantially increased atrial natriuretic peptide (48.8 +/- 8.9 to 85.8 +/- 13.0) and antidiuretic hormone (3.4 +/- 0.3 to 4.6 +/- 0.5) levels, whereas renin decreased (0.9 +/- 0.1 to 0.8 +/- 0.2) slightly but not significantly. Iopromide did not induce substantial changes in the other vasoactive peptides or in allergy-mediated substances after the contrast medium was injected. Similarly, cardiovascular parameters (heart rate, pulmonary and systemic blood pressures, and results of electrocardiogram) also remained unchanged after contrast injection. CONCLUSION: Iopromide caused no appreciable hemodynamic alterations associated with the changes in atrial natriuretic peptide and antidiuretic hormone and no evidence of allergy-mediated reactions in all volunteers.

Adult↗
PubMed1997

Experimental treatments for asthma.

There has been increased recognition of the importance of inflammatory cells and their products in the pathogenesis of asthma. From this recognition has evolved a number of new approaches to treat the various components of the asthmatic inflammatory response. Nonselective anti-inflammatory agents such as cyclosporine and gold appear to decrease symptoms and allow a steroid-sparing effect in many cases, though side effects from cyclosporine often necessitate dose reduction. Novel oral compounds as the 5-lipoxygenase inhibitors have been effective in controlling asthma symptoms triggered by various stimuli, and the cysteinyl leukotriene receptor antagonists have shown promise in this regard as well. Neurokinin antagonists, inhaled loop diuretics, and lidocaine may play significant roles in asthma therapy through inhibition of neurogenic inflammation and possibly mast cell function. Inhibition of mast cell products by existing drugs such as heparin or the development of specific inhibitors of mast cell tryptase may also be effective agents, as are selective phosphodiesterase inhibitors, which appear to have anti-inflammatory properties. Finally, specific cytokine antagonists, agonists, inhibitors of T-cell function, selective inducible nitric oxide synthase inhibitors, and even gene-directed strategies may provide not only insights into the pathogenesis of asthma but also novel therapeutic approaches to treat the inflammation in this disease.

Administration, Inhalation↗
PubMed2002

The stem cell factor-c-kit system and mast cells in human pancreatic cancer.

Stem cell factor (SCF) and its receptor c-kit take part in the regulation of developmental processes of mast cells, hematopoietic stem cells, and melanocytes, as well as in the growth control of human malignancies. To explore the possible role of the SCF-c-kit system and of mast cells in pancreatic cancer, the concomitant expression and distribution of the two molecules were examined in 17 normal and 26 cancerous human pancreatic tissues and in 6 cultured pancreatic cancer cell lines. Mast cell distribution was also evaluated in the same tissue samples. In addition, the effects of SCF and of the c-kit tyrosine-kinase inhibitor STI571 on the growth of the cancer cell lines and of the normal pancreatic ductal cell line TAKA-1 were assessed. SCF immunoreactivity was absent in acinar, ductal, and islet cells of the normal pancreas and faint in pancreatic cancer tissues and cell lines. In contrast, c-kit was clearly present in some normal and hyperplastic ducts of the normal pancreas, in the cancer cells of 73% of the tumor samples, and in all the cell lines tested. Mast cells, identified by tryptase and chymase immunostaining on consecutive tissue sections, showed immunoreactivity for SCF and c-kit in both normal and cancerous specimens and their number was significantly increased (p = 0.03) in pancreatic cancer compared with the normal pancreas. SCF showed a dose-dependent growth inhibitory effect on TAKA-1 cells (p < 0.001), whereas pancreatic cancer cells were resistant to the SCF-induced growth inhibition. Nonetheless, the growth of TAKA-1 cells and pancreatic cancer cells was inhibited by the c-kit tyrosine kinase inhibitor STI571. In conclusion, the SCF-c-kit system, possibly with the contribution of mast cells, may have a growth-regulating role in the normal pancreas, which is altered during malignant transformation.

Adolescent↗
PubMed1999

Inflammatory mast cells up-regulate angiogenesis during squamous epithelial carcinogenesis.

Expression of HPV16 early region genes in basal keratinocytes of transgenic mice elicits a multistage pathway to squamous carcinoma. We report that infiltration by mast cells and activation of the matrix metalloproteinase MMP-9/gelatinase B coincides with the angiogenic switch in premalignant lesions. Mast cells infiltrate hyperplasias, dysplasias, and invasive fronts of carcinomas, but not the core of solid tumors, where they degranulate in close apposition to capillaries and epithelial basement membranes, releasing mast-cell-specific serine proteases MCP-4 (chymase) and MCP-6 (tryptase). MCP-6 is shown to be a mitogen for dermal fibroblasts that proliferate in the reactive stroma, whereas MCP-4 can activate progelatinase B and induce hyperplastic skin to become angiogenic in an in vitro bioassay. Notably, premalignant angiogenesis is abated in a mast-cell-deficient (KITW/KITWWv) HPV16 transgenic mouse. The data indicate that neoplastic progression in this model involves exploitation of an inflammatory response to tissue abnormality. Thus, regulation of angiogenesis during squamous carcinogenesis is biphasic: In hyperplasias, dysplasias, and invading cancer fronts, inflammatory mast cells are conscripted to reorganize stromal architecture and hyperactivate angiogenesis; within the cancer core, upregulation of angiogenesis factors in tumor cells apparently renders them self-sufficient at sustaining neovascularization.

Animals↗
PubMed1991

Biochemical diagnosis of systemic mast cell disorders.

Systemic mastocytosis is characterized by an abnormal proliferation of tissue mast cells. Symptoms of mastocytosis are primarily attributed to the release of mast cell mediators during episodes of systemic activation of the excessive numbers of mast cells. Thus, biochemical evidence for the release of increased quantities of mast cell secretory products can suggest or confirm, depending on the clinical situation, a diagnosis of systemic mastocytosis. A major advantage of the biochemical approach to the diagnosis of systemic mast cell disease is that it has allowed the recognition of a class of patients in whom episodes of systemic mastocyte activation can be unequivocally documented biochemically but in whom clear-cut evidence of abnormal mast cell proliferation is lacking by current histologic criteria. Although the release of increased quantities of mast cell mediators can be demonstrated during episodes of mast cell activation in such patients, mediator levels are usually normal at quiescent times. By contrast, patients with proliferative mast cell disease (mastocytosis) usually exhibit chronic overproduction of mast cell mediators. Mast cell secretory products that can be measured in an attempt to obtain biochemical evidence of systemic mast cell activation include histamine, prostaglandin D2, tryptase, and heparin. The analytical approaches to assessing release of those individual mast cell products are evaluated. In general, the diagnosis and investigation of patients with systemic mast cell activation can best be accomplished by concerted use of histologic examination of key tissues together with analysis of chemical markers of the mast cell.

Flushing↗
PubMed1993

Identification of basophils by immunohistochemistry in the airways of post-mortem cases of fatal asthma.

There is increasing evidence for the role of basophils in the pathogenesis of bronchial asthma. To examine the presence of basophils in the airways of patients with fatal asthma by immunohistochemistry, we stained lung tissues from four post-mortem cases who had died from severe asthmatic attacks and four controls with a monoclonal antibody raised against tryptase (AA-1) and anti-IgE. Mast cells and basophils were identified in the bronchioles as AA-1- and anti-IgE-positive cells, and anti-IgE-positive cells, respectively. Airway mast cells were found beneath the basement membrane, near blood vessels in the submucosa, and adjacent to the submucosal glands, and scattered throughout the muscle bundles. There was a significant increase of mast cells in the asthma group compared with the control group (203.5+/-84.6/mm2, mean+/-s.d. vs 37.7+/-8.7/mm2, P<0.05, n=4). In contrast, basophils were observed in the airway lumen, in the bronchial epithelium and in the submucosa. The number of basophils in the bronchioles was 81.8+/-55.5/mm2 (n = 4); however, basophils were not found at all in the airways of the control group. Although eosinophils, B lymphocytes and macrophages bear low affinity IgE receptors and could react with anti-IgE, the location of these cells in the close sections did not correspond closely with basophils. The presence of basophils in lung tissues obtained from fatal asthma patients supports the view that basophils play a role in the pathogenesis of bronchial asthma.

Adult↗
PubMed1994

Nasal challenge shows pathogenetic relevance of specific IgE serum antibodies for nasal symptoms caused by hexahydrophthalic anhydride.

Hexahydrophthalic anhydride (HHPA) is a component of some epoxy resin systems. A high fraction of HHPA-exposed workers display nasal symptoms, and some of them have specific serum antibodies. To test the pathogenetic relevance of the antibodies nasal challenge tests were performed with a conjugate of HHPA and human serum albumin (HSA) at three increasing concentrations. Eleven subjects, who were IgE-sensitized against HHPA (positive in RAST and in skin-prick test against the HHPA-HSA conjugate), and who reported work-related nasal symptoms, had a significant increase of nasal symptoms and a decrease of nasal inspiratory peak flow after the challenges. The symptoms were associated with specific serum IgE, but with IgG. Further, significant increases were found in eosinophil and neutrophil counts, and in levels of tryptase, and albumin, whereas no clear rise was recorded for eosinophil cationic protein in nasal lavage fluid. Nine subjects, who were not sensitized, but who complained of work-related nasal symptoms, and 11 subjects, who were not sensitized and had no symptoms, displayed no significant change in any of these parameters. It is concluded that the symptoms in some of the workers were caused by an IgE-mediated mast cell degranulation, followed by an inflammatory reaction, engaging eosinophil and neutrophil cells.

Adult↗
PubMed1995

TNF alpha is localized to nasal mucosal mast cells and is released in acute allergic rhinitis.

Allergic mucosal inflammation is characterized by tissue infiltration with eosinophils, and associated activation of mast cells and T lymphocytes. Tumour necrosis factor (TNF) alpha/cachectin is a candidate cytokine relevant to the pathogenesis of these events through its capacity to upregulate the expression of endothelial cell adhesion molecules, mediate granulocyte chemoattraction, and activate eosinophils, mast cells and T cells. To investigate the presence and localization of TNF alpha in the nasal mucosa in allergic rhinitis, nasal biopsies from perennial rhinitic (n = 13) and non-rhinitic volunteers (n = 11) were embedded in glycol methacrylate and immunostained with a monoclonal antibody directed against TNF alpha, and adjacent 2 microns sections stained for tryptase, CD3 and eosinophil cationic protein. This identified positive immunostaining for TNF alpha in the submucosa of both the rhinitic and normal subjects (median cell counts 13 and 23 cells/mm2 respectively, P = 0.24) with cellular localization to mast cells but not to T-lymphocytes or eosinophils. In a subsequent study of seven atopic subjects, nasal allergen challenge produced increases in lavage levels of histamine and albumin, which was associated with significant release of TNF alpha as early as 2 min post-allergen when compared with the saline control day (P = 0.05). This difference was also apparent when studying the area under the curve both at 30 and 60 min post-challenge t-test (P = 0.015 and 0.02 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2006

Induction of interleukin-6 release from monocytes by serine proteinases and its potential mechanisms.

Serine proteinases have been recognized playing an important role in inflammation via proteinase-activated receptors (PAR). However, little is known of the influence of serine proteinases and PAR on interleukin-6 (IL-6) secretion from highly purified monocytes. We challenged monocytes from human peripheral blood with serine proteinases and agonist peptides of PAR and measured the levels of IL-6, IL-1beta and IL-12 in culture supernatants by enzyme-linked immunosorbent assay. The results showed that thrombin, trypsin, tryptase and elastase stimulated approximately up to 2.9-, 2.0-, 1.8- and 2.1-fold increase in IL-6 release from monocytes following 16 h of incubation, respectively. Proteinase inhibitors inhibited the actions of proteinases on monocytes. Agonist peptides of PAR-1 (SFLLR-NH(3)) and PAR-4 (GYPGQV-NH(2)), but not PAR-3 (TFRGAP-NH(2)), also induced IL-6 release from monocytes. The proteinases and agonists of PAR failed to stimulate IL-1beta and IL-12 secretion. In conclusion, the induction of IL-6 secretion by serine proteinases may be through the activation of PAR.

Blood Cells↗