Wool and grain dusts stimulate TNF secretion by alveolar macrophages in vitro.

OBJECTIVE: The aim of the study was to investigate the ability of two organic dusts, wool and grain, and their soluble leachates to stimulate secretion of tumour necrosis factor (TNF) by rat alveolar macrophages with special reference to the role of lipopolysaccharide (LPS). METHODS: Rat alveolar macrophages were isolated by bronchoalveolar lavage (BAL) and treated in vitro with whole dust, dust leachates, and a standard LPS preparation. TNF production was measured in supernatants with the L929 cell line bioassay. RESULTS: Both wool and grain dust samples were capable of stimulating TNF release from rat alveolar macrophages in a dose-dependent manner. The standard LPS preparation caused a dose-dependent secretion of TNF. Leachates prepared from the dusts contained LPS and also caused TNF release but leachable LPS could not account for the TNF release and it was clear that non-LPS leachable activity was present in the grain dust and that wool dust particles themselves were capable of causing release of TNF. The role of LPS in wool dust leachates was further investigated by treating peritoneal macrophages from two strains of mice, LPS responders (C3H) and LPS non-responders (C3H/HEJ), with LPS. The non-responder mouse macrophages produced very low concentrations of TNF in response to the wool dust leachates compared with the responders. CONCLUSIONS: LPS and other unidentified leachable substances present on the surface of grain dust, and to a lesser extent on wool dust, are a trigger for TNF release by lung macrophages. Wool dust particles themselves stimulate TNF. TNF release from macrophages could contribute to enhancement of inflammatory responses and symptoms of bronchitis and breathlessness in workers exposed to organic dusts such as wool and grain.     

Some opinions on byssinosis in China

On the basis of some study results in China and reports from abroad, a conclusion should be drawn that leads to the recognition of a pneumoconiosis-like lesion of interstitial fibrosis. This disease is called "cotton pneumoconiosis" and we may classify these occupational lesions into four types: 1) byssinosis; 2) chronic obstructive pulmonary disease (COPD); 3) cotton fever; and 4) cotton pneumoconiosis. Byssinosis, COPD, cotton fever and cotton pneumoconiosis may be different types of responses due to the different duration of exposure, the different parts of bronchial tree (upper respiratory tract, small airway, and respiratory part) where deposition occurs, and the different components of cotton dust (broken cotton fibers, bracts, pericarps, bacteria, and fungi). These responses, which include histaminelike reaction, allergy, and stimulation of foreign material, happen in different symptoms of the syndrome among cotton mill workers. But no matter whether responses caused by inhalation of dust are inflammation or allergic reaction, cotton dust is foreign stimulation on deposited sites, causing lung fibrosis after lung stimulation. For the health of cotton workers, we must pay attention not only to the acute effects but also to the chronic lesions. We therefore suggest that these four types of occupational lung disorders caused by inhalation of cotton dust may be called by the joint name, "Byssinosis syndrome."     

Stimulation and release of prostaglandins and thromboxane from macrophages by cotton dust associated lipopolysaccharides

Decreases in the ventilation capacity of human lungs following the inspiration of cotton dust correlates more closely with the concentration of endotoxin in the dust than with any other parameter measured thus far. A lipopolysaccharide isolated from the endotoxin of Enterobacter agglomerans, a common bacterial contaminant of cotton fiber, stimulated isolated rat macrophages to produce and release prostaglandins 6 keto-PGF1 alpha, PGF2 alpha, PGE2, PGD2, PGA2, and PGB2 and thromboxane B2. If in vivo human pulmonary macrophages respond in a similar fashion by releasing these arachidonic acid metabolites or their immediate precursors in response to stimulation by cotton dust associated lipopolysaccharides, some of the acute pulmonary changes observed in humans following inspiration of cotton dust could be caused by increased release of these biologically active compounds. Daily release of arachidonic acid metabolites at concentrations significantly above normal homeostatic levels could produce some of the pathophysiologic pulmonary changes observed in byssinotics. This paper reports the results of an experiment to quantitate arachidonic acid metabolite production following macrophage stimulation by E. agglomerans lipopolysaccharide. Procedures are described for the stimulation of macrophages by cotton dust associated lipopolysaccharide, for the separation and identification of arachidonic acid and its metabolites by high-performance liquid chromatography, and for the quantification of those products by radioisotope techniques.     

Histamine release from mast cells by terpenoid aldehydes isolated from glanded varieties of cotton

In vivo and in vitro experiments have strongly indicated that mast cell degranulation, with its release of histamine and other pharmacoactive compounds, plays a major role in the acute respiratory response of humans following inhalation of cotton textile dust. Thirteen terpenoid aldehydes isolated from the glands of the two major Gossypium species used for cotton production, stimulated significant release of histamine from mast cells at concentrations of 1 micrograms/mL. Eleven of the thirteen compounds produce significant mast cell degranulation at concentrations well below the levels of free terpenoid aldehydes that could be expected to enter the lungs during an eight hour work day under the current permissible card room standards of 200 micrograms per cubic meter. Daily mast cell degranulation, stimulated by these terpenoid aldehydes could account for many of the pathophysiological changes found in the chronic byssinotic.     

Histamine induction and release following proteolytic enzyme exposure.

The mechanism of biologic response from exposure to a 12% subtilisin Carlsberg preparation is shown to be one of histamine release in the guinea pig. Three groups of guinea pigs were pretreated by intradermal injections withsaline solution of (1) the commercial proteolytic enzyme preparation containing 12% subtilisin Carlsberg, (2) an alkaline protease preparation obtain from Aspergillus oryzae that was isolated from cotton dust, or (3) a nonproteolytic mixture of proteins and lipases obtained from cotton seeds. The histamine content of the ling, liver, and ear tissues of guinea pigs that were pretreated with any one of the three preparations showed an in untreated animals. Following challenge by intratracheal injection of a saline solution containing the subtilisin preparation, the guinea pigs pretreated with the same preparation showed a markedly reduced liver histamine level. Challenge by inhalation exposure to the subtilisin preparation of guinea pigs that were pretreated with any one of the above preparations resulted in a lower histamine concentration in the lungs and livers.     

Histamine release by Western red cedar (Thuja plicata) from lung tissue in vitro

Evans, Elizabeth and Nicholls, P. J. (1974).British Journal of Industrial Medicine,31, 28-30. Histamine release by Western red cedar(Thuja plicata)from lung tissue in vitro. Various respiratory symptoms have previously been observed in workers exposed to dust from Western red cedar (Thuja plicata). Although an allergic basis for these effects has been proposed, the possibility that the dust may contain a pharmacologically active agent was investigated. Aqueous extracts of two samples of red cedar released significant amounts of histamine from pig and human lung in vitro. For one of these samples, using pig lung, a dose-response relation was found over a narrow range of concentrations. These dusts possessed the same order of histamine-releasing activity as a sample of cotton dust. Potassium cyanide reduced the release of histamine caused by low concentrations of Western red cedar. Similar effects of cyanide on the histamine-releasing activity of cotton dust and compound 48/80 were observed. It is possible that release of histamine in the lungs and upper respiratory tract occurs on inhalation of dust from Western red cedar and this may be a contributory factor to the development of respiratory symptoms in workers exposed to the dust of this wood.     

Histamine release from platelets for assay of byssinogenic substances in cotton mill dust and related materials.

Previous reports suggest that byssinosis, an asthma-like condition among textile workers, may be mediated in part by histamine liberated following inhalation of dust. A simple, sensitive, and reliable procedure using pig platelets which contain the unusually high concentration of 0.8-1.6 microgram histamine/10(9) cells has been devised for the assay of histamine-releasing factors in cotton mill dust and related materials, and has yielded results generally in accordance with earlier assays using chopped lung tissue. As little as 50--100 microgram of total extractable substances from cotton mill dust can be measured. The activity of the extract is associated with the non-dialysable high molecular weight portion. However, conditions of acid hydrolysis do not destroy the activity. Extracts of leaves from different varieties of plant are highly potent, which suggests that the factors responsible for byssinosis are widely distributed plant components, present in textile fibre plants and converted to a respirable form by handling processes. Ellagic acid and sodium metasilicate release histamine from pig platelets, and represent new classes of compounds with possible roles in the aetiology of byssinosis.     

Histamine release from platelets for assay of byssinogenic substances in cotton mill dust and related materials.

Previous reports suggest that byssinosis, an asthma-like condition among textile workers, may be mediated in part by histamine liberated following inhalation of dust. A simple, sensitive, and reliable procedure using pig platelets which contain the unusually high concentration of 0.8-1.6 microgram histamine/10(9) cells has been devised for the assay of histamine-releasing factors in cotton mill dust and related materials, and has yielded results generally in accordance with earlier assays using chopped lung tissue. As little as 50--100 microgram of total extractable substances from cotton mill dust can be measured. The activity of the extract is associated with the non-dialysable high molecular weight portion. However, conditions of acid hydrolysis do not destroy the activity. Extracts of leaves from different varieties of plant are highly potent, which suggests that the factors responsible for byssinosis are widely distributed plant components, present in textile fibre plants and converted to a respirable form by handling processes. Ellagic acid and sodium metasilicate release histamine from pig platelets, and represent new classes of compounds with possible roles in the aetiology of byssinosis.     

Histamine-related reactions in patients with byssinosis

The purpose of the study was to analyze the mechanism of histamine action in histamine-dependent reactions of neutrophils and lymphocytes in patients with byssinosis and chronic asthmatic bronchitis under cotton and flax dust effect. The appraisal of histamine content in blood serum, receptor/histamine distribution of lymphocyte and neutrophil subpopulations (rosette-forming double and triple reactions), determination of histamine modeling effect on lymphocyte-neutrophil cooperation in the inhibition reaction of leukocyte migration revealed that under cotton dust effect neutrophils and the complement system were involved into the histamine liberation process in byssinosis patients, lymphocytes were most likely not involved into the process. Flax dust-affected histamine reactions were not so distinct: lymphocyte and neutrophil reactivity in byssinosis patients did not exceed the standards. Patients with chronic asthmatic bronchitis had high blood concentration of histamine and experienced some changes in cells' migration characteristics. It was assumed that primarily nonimmune mechanisms of histamine liberation and activation of the complement system were involved into byssinosis pathological process in patients exposed to cotton and flax dust effect. In patients with chronic asthmatic bronchitis there occurred all 3 activation mechanisms of biologically active substances, i.e., allergic and nonantigenic ways of histamine liberation and activation of the complement system.     

Effects of fly ash inhalation on murine immune function: Changes in macrophage-mediated activities

Mice were exposed to fly ash particles (<2.1 μm diameter) by inhalation for variable amounts of time at concentrations ranging from 535 to 2221 μg/m³. This fine fraction was approximately 32% by weight of the total dust generated. The effects of these exposures were assessed on macrophage-mediated functions. Phagocytosis of bacterial cells by the alveolar macrophages was depressed in the fly ash-exposed animals as was the ability to enhance T-cell mitogenesis. Fly ash exposure failed to produce a significant change in the cellular immune response (delayed-type hypersensitivity reaction) to antigenic challenge in the lungs of sensitized animals.     

二氧化硅通过肺泡巨噬细胞的识别反应

矽肺是指长期接触二氧化硅粉尘后,潴留肺内的粉尘引起的以肺组织慢性持续性炎症与进行性纤维化为主要病理特点的全身性疾病,其基本病理变化过程为肺泡炎、肺肉芽肿、肺纤维化。肺泡巨噬细胞介导的固有免疫在矽肺炎性反应中起着重要的作用：由于吸入性二氧化硅尘粒形态十分类似病原体相关分子模式（PAMPs）或危险相关分子模式（DAMPs）,可引起肺泡巨噬细胞的清道夫受体（SR）、Toll样受体（TLRs）或核苷酸结合寡聚化结构域（NOD）样受体（NLRs）等模式识别受体（PRRs）识别,从而通过激活胞内NLRP3炎性体,介导肺泡巨噬细胞的细胞焦亡（pyroptosis）,进而释放白介素、前列腺素等促炎因子,导致肺组织炎性反应;与此同时,部分活化的肺泡巨噬细胞还会发挥抗原递呈作用,启动T细胞免疫机制,加剧肺内炎性反应,最终导致肺组织纤维化。     

Characterisation of textile dust extracts: I. Histamine release in vitro.

Cotton, flax, hemp, and cotton bracts extracts did not release histamine from mouse, rat, guinea pig, horse, cow, and monkey lung. Neither rat peritoneal mast cells nor mouse mastocytoma cells released histamine when incubated with textile dust extracts. Compound 48/80 caused a considerable release of histamine from all these tissues and the extracts released histamine from pig and human lung tissues. Whereas dusts that cause bronchospasm in man released histamine--for instance, cotton--those that are inactive, such as pericarps, did not. Histamine release was not quantitatively related to the concentration of extract used. Cotton bracts extract released histamine from pig lung tissue whereas in the same preparations methyl piperonylate was inactive. The active releasing agent was highly water soluble but could not be steam distilled from, nor extracted by, ether from bracts extract. These physicochemical properties are not characteristic of methyl piperonylate. There was no correlation between the induction of histidine decarboxylase and the histamine releasing capacity of the extracts. We conclude that pig lung is a useful qualitative assay tissue for the further characterisation of the histamine releasing agent(s) in textile dust extracts.     

Characterisation of textile dust extracts: I. Histamine release in vitro

Cotton, flax, hemp, and cotton bracts extracts did not release histamine from mouse, rat, guinea pig, horse, cow, and monkey lung. Neither rat peritoneal mast cells nor mouse mastocytoma cells released histamine when incubated with textile dust extracts. Compound 48/80 caused a considerable release of histamine from all these tissues and the extracts released histamine from pig and human lung tissues. Whereas dusts that cause bronchospasm in man released histamine--for instance, cotton--those that are inactive, such as pericarps, did not. Histamine release was not quantitatively related to the concentration of extract used. Cotton bracts extract released histamine from pig lung tissue whereas in the same preparations methyl piperonylate was inactive. The active releasing agent was highly water soluble but could not be steam distilled from, nor extracted by, ether from bracts extract. These physicochemical properties are not characteristic of methyl piperonylate. There was no correlation between the induction of histidine decarboxylase and the histamine releasing capacity of the extracts. We conclude that pig lung is a useful qualitative assay tissue for the further characterisation of the histamine releasing agent(s) in textile dust extracts.     

Role of histamine in the aetiology of byssinosis. II. Lung histamine concentrations in guinea pigs chronically exposed to cotton and flax dusts.

Data presented in this study support the finding that cotton and flax dusts contain agents which potentiate the formation or accumulation of histamine or both in the lungs of guinea pigs exposed to dust, and that such agents are present at much higher levels in cotton dust than in flax dust. The potentiating effect may be through the recruitment of mast cells into the lung. Both cotton and flax dusts contain methylating enzyme inhibitory agents, whereas cotton dust also contains agents that inhibit histaminase activity; flax dust contains agents potentiating histamine activity. These agents working together result in the accumulation or depletion of histamine observed in the different groups of animals exposed to either cotton or flax dust in this study.     

Role of histamine in the aetiology of byssinosis. I Blood histamine concentrations in workers exposed to cotton and flax dusts

The formation or the accumulation, or both, of histamine in the lungs may be potentiated by agent(s) present in cotton dust at higher level(s) than in flax dust and negligible in cottonseed dust. It has been suggested that such potentiation may be due to the activation of the ability of the lung to produce histamine and/or produce or recruit mast cells; this may present an acceptable explanation of the mechanism by which the propagation of the chronic effect of the dust proceeds in cotton and flax workers. Histamine accumulated in the lung over the weekend is released on exposure to dust causing the symptoms of byssinosis. The difference in the rate of histamine metabolism relative to the rate of histamine formation in byssinotic subjects leads to a more prolonged histamine accumulation than in symptom free subjects, with the consequent appearance of the symptoms of byssinosis. Continuous exposure to dust, without weekend interruption, leads to equivalent rates of histamine formation and metabolism with non-considerable histamine accumulation in the lungs and consequent absence of the symptoms of byssinosis.     

Some Pharmacological Actions of Cotton Dust and Other Vegetable Dusts

Aqueous extracts of cotton and other vegetable dusts cause contraction of the isolated ileum and tracheal muscle of the guinea-pig, and of isolated human bronchial muscle. The levels of this contractor activity place the dusts of cotton, flax, and jute in the order of the probable incidence of byssinosis occurring in the mills spinning these fibres.

Extracts of cotton dust possess a histamine-liberating activity and contain a permeability-increasing component. These actions are of plant origin and are found in the pericarp and bracts of the cotton boll. Histamine and 5-hydroxytryptamine have also been found in some cotton dust samples. The formation of histamine by bacterial action in cotton dust does not take place under conditions found in cotton mills. The smooth muscle contractor substance is organic in nature, relatively heat-stable, and dialysable. The relevance of these results to the symptoms of byssinosis is discussed.

     

Role of histamine in the aetiology of byssinosis. I Blood histamine concentrations in workers exposed to cotton and flax dusts.

The formation or the accumulation, or both, of histamine in the lungs may be potentiated by agent(s) present in cotton dust at higher level(s) than in flax dust and negligible in cottonseed dust. It has been suggested that such potentiation may be due to the activation of the ability of the lung to produce histamine and/or produce or recruit mast cells; this may present an acceptable explanation of the mechanism by which the propagation of the chronic effect of the dust proceeds in cotton and flax workers. Histamine accumulated in the lung over the weekend is released on exposure to dust causing the symptoms of byssinosis. The difference in the rate of histamine metabolism relative to the rate of histamine formation in byssinotic subjects leads to a more prolonged histamine accumulation than in symptom free subjects, with the consequent appearance of the symptoms of byssinosis. Continuous exposure to dust, without weekend interruption, leads to equivalent rates of histamine formation and metabolism with non-considerable histamine accumulation in the lungs and consequent absence of the symptoms of byssinosis.     

Mechanisms of allergy and chemical sensitivity.

Allergy and chemical sensitivity are closely related disorders in which environmental exposures produce inflammatory reactions. For allergy, environmental proteins bind to IgE antibody on mast cells leading to the release of inflammatory mediators. In chemical sensitivity, low molecular weight chemicals bind to chemoreceptors on sensory nerve C-fibers leading to the release of inflammatory mediators. Clinical manifestations are similar in the two conditions. The overlap between the two conditions has a basis in mechanism, so the similarity of clinical manifestations and high percentage of individuals with both conditions may have a biological basis. Chronic exposures can lead to adaptation phenomena. Depression has been associated with both allergy and chemical sensitivity. Both the allergic and chemical irritant responses may be subjected to conditioning so that the response is triggered by other stimuli. Evidence for conditioning is strongest for allergy. Both allergy and chemical sensitivity can be acquired in association with irritant exposures.     

Fever of Undetermined Etiology after Cleaning of Steam Turbine Condensers

Two outbreaks of a febrile syndrome marked by chills, headaches, myalgia, nausea, and malaise occurred in workers who had cleaned the steam condensers of electric power turbines. Mean incubation period was 38 hours. Twenty-two of twenty-three exposed men became ill. Clinical and environmental investigation failed to reveal the etiology of the outbreaks. The circumstances and clinical syndrome have points of similarity to fever following inhalation of metal fumes and low-grade, stained cotton dust, and to Pontiac fever.     

Effects of fish oil on the neuro-endocrine responses to an endotoxin challenge in healthy volunteers

BACKGROUND & AIMS: Fish oil (FO) has been shown to modulate the acute and chronic inflammatory responses. Endotoxin (LPS) has been shown to mimic several aspects of sepsis. The study aimed at testing the effects of oral FO supplements in healthy subjects submitted to intravenous LPS on systemic and endocrine response. SUBJECTS AND METHODS: Fifteen healthy men (aged 26.0+/-3.1 years, BMI 23.8+/-1.9 kg/m2), were enrolled. Subjects were randomised to 3-4 weeks of oral FO supplementation (7.2 g/day, providing 1.1 g/day of 20:5 (n-3) and 0.7 g/day of 22:6 (n-3) fatty acids) or no supplementation and then submitted to endotoxin challenge: 2 ng/kg of LPS. All subjects were studied twice (placebo and LPS). Measurements: vital signs, energy expenditure (EE), glucose and lipid metabolism ((2)H2-glucose), plasma cytokines and stress hormones for 6 h after LPS or placebo. RESULTS: LPS caused cytokine release, fever, increases in heart rate, resting EE and substrate oxidation, plasma glucagon and glucose concentrations; the neuro-endocrine response was characterised by increased plasma stress hormones. FO significantly blunted fever, ACTH and cortisol plasma levels (no effect on cytokine release). FO blunted the peak norepinephrine after LPS. CONCLUSION: FO supplements blunted the endocrine stress response and the increase in body temperature, but had no impact on cytokine production after LPS. These findings conflict with the postulated anti-inflammatory effects of FO on arachidonic acid metabolism and cytokine release. These results suggest that FO may exert beneficial effects in sepsis though non-inflammatory which require further investigations.