Chemical immunology and allergy最新文献

The term anaphylaxis was coined by Charles Richet and Paul Portier when they tried to immunize dogs with actinia extracts, but after a repeated injection of a small amount of the toxin the dog died within 25 min. The new term rapidly spread all over the world. The discovery of the phenomenon of anaphylaxis showed that by immunization not only protection but also harmful events could be induced. For this discovery Richet received the Nobel Prize in 1913, but he still believed the condition of anaphylaxis was a lack of protection to the poisonous effect of the substance. Already earlier similar clinical phenomena had been observed but not well described. A major breakthrough in understanding the pathophysiology came through the experiments of Dale and Laidlaw who showed that the newly discovered histamine was able to induce quite similar symptoms to anaphylaxis. For decades reactions mimicking anaphylaxis but without involvement of the immune systems were called 'anaphylactoid', 'allergy-like' or 'pseudo-allergic'. Since the new definition of the World Allergy Organization (WAO) anaphylaxis is defined on the basis of clinical symptoms independent of pathomechanisms involved: one distinguishes between allergic and non-immune anaphylaxis. Epinephrine (Adrenalin) was soon recognized as treatment of choice of this dramatic condition.

Neuropilins (NRPs) are co-receptors for class 3 semaphorins and for members of the vascular endothelial growth factor (VEGF) family of angiogenic cytokines. Genetic analysis of the role of NRPs in mice shows that NRP1 is essential for embryonic neuronal pathfinding and cardiovascular development, mediated via semaphorins and VEGF, respectively, while NRP2 has a more restricted role in neuronal patterning and lymphangiogenesis. NRPs are thought to mediate functional responses, most importantly cell migration, as a result of complex formation with other receptors, such as plexins in the case of semaphorins and the VEGF receptor, VEGFR2, resulting in enhanced signalling via some intracellular pathways. Recent findings indicate that NRPs may have important biological roles in other physiological and disease-related processes. In particular, NRPs are highly expressed in diverse tumour cell lines and human neoplasms and have been implicated in several biological processes regulating tumour growth in vivo, suggesting that NRP1 may be a future therapeutic target in cancer.

Increasing data from the literature point to a neutrophil-mediated role via cytokine production in several aspects of mammalian biology, including angiogenesis. In such regard, neutrophils have been shown to synthetize and release a number of molecules able to promote, directly or indirectly, the growth and migration of endothelial cells, in turn inducing the formation of new blood vessels from preexisting ones. Interestingly, neutrophil-derived cytokines can be involved either in physiological or in pathological angiogenesis, depending on either the functioning or dysregulation of sophisticated interplays among different cell types, extracellular matrix and soluble mediators within the microenvironment. Our review resumes the most interesting studies elucidating the role of neutrophil-derived cytokines in human physiological and pathological angiogenesis. When appropriate, supporting observations generated in animal models will be also mentioned. Particular emphasis will be given to VEGF and PK2/Bv8, rather than CXCL8/IL-8 and OSM. We will also discuss the potential role of neutrophil-derived cytokines such as FGF2, Ang1 and IL-17, whose roles in angiogenesis - albeit anticipated - remain to be elucidated.

White adipose tissue constantly experiences expansion and shrinkage during the entire adulthood, depending on the metabolic status of the host. Emerging evidence demonstrates that the plasticity of white adipose tissue is tightly controlled by the adipose vasculature, which may grow or regress to coordinate adipose tissue metabolism. In metabolically active brown adipose tissue, an exceedingly high density of blood vessels may perfuse oxygen for energy consumption. Consequently, modulation of vascular density and functions in both white adipose tissue and brown adipose tissue may offer an exciting opportunity for therapeutic interference of obesity and metabolic disease. In fact, in several preclinical obese animal models, angiogenesis modulators significantly alter body weights and metabolic rates of the host, implying a possible new therapeutic option for treatment of these common human diseases. Additionally, angiogenesis modulators may significantly regulate insulin sensitivity and the development of type II diabetes. In fact, antiangiogenic or angiogenic drugs have been implicated for treatment of diabetes and diabetes-related complications. Given the therapeutic values of angiogenesis modulators in preclinical animal models, it is reasonable to speculate these angiogenesis modulators may eventually be used for treatment of human obesity and metabolic disorders.

Angiogenesis is a constant hallmark of multiple myeloma progression and has prognostic potential. Multiple myeloma cells interact with surrounding host cells and extracellular matrix, this crosstalk affecting the most important aspects of the malignant phenotype, both at primary and secondary tumor sites. The pathophysiology of multiple myeloma-induced angiogenesis involves both direct production of angiogenic cytokines by plasma cells and their induction within the bone marrow microenvironment cells. A direct involvement of bone marrow macrophages and mast cells in vasculogenic mimicry has been demonstrated, thus contributing together with circulating endothelial cells and endothelial precursor cells to the multiple myeloma neovascularization. The role of host cells or the niche microenvironment and extracellular matrix represents an intense area of research, finalized at a better understanding of the pathophysiological modifications of the complete tumor entity, i.e. malignant cells and microenvironment.

The chromones are a class of chemical compounds characterised by the presence of the structure 5:6 benz-1:4-pyrone in their chemical make-up. The first chromone in clinical use, khellin, was extracted from the seeds of the plant Ammi visnaga, and had been used for centuries as a diuretic and as a smooth muscle relaxant. Its use in bronchial asthma was reported in 1947. In the 1950s, Benger's Laboratories embarked on a research programme to synthesise and develop modifications of khellin for the treatment of asthma. New compounds were screened using animal models to test the ability of the compound to prevent the anaphylactic release of histamine and SRS-A (leukotrienes) from sensitised guinea pig lung, and a human model to check the ability to reduce the bronchoconstriction induced by inhaled antigen bronchial challenge. For initial screening the human work was undertaken by Dr. R.E.C. Altounyan, who suffered from allergic bronchial asthma and was employed by Benger's Laboratories. After 8 years and more than 600 challenges using over 200 compounds, in 1965 Altounyan arrived at disodium cromoglycate (DSCG), the chromone that met the criteria of providing more than 6 h of protection. DSCG is still used today as a mast cell stabiliser.

In this chapter we will first consider whether there is real evidence on the basis of literature for early descriptions in antiquity of pathogenic reactions after food intake that could be comparable to allergy, for instance in the scriptures of Hippocrates or Lucretius. On this topic we are skeptical, which is in agreement with the medical historian Hans Schadewaldt. We also assert that it is unlikely that King Richard III was the first food-allergic individual in medical literature. Most probably it was not a well-planned poisoning ('allergy') with strawberries, but rather a birth defect ('… his harm was ever such since his birth') that allowed the Lord Protector to bring Mylord of Ely to the scaffold in the Tower, as we can read in The History of King Richard III by Thomas More (1478-1535; published by his son-in-law, Rastell, in 1557). In 1912, the American pediatrician Oscar Menderson Schloss (1882-1952) was probably the first to describe scratch tests in the diagnosis of food allergy. Milestones in the practical diagnosis of food allergy are further discussed, including scratch tests, intradermal tests, modified prick tests and prick-to-prick tests. False-negative results can be attributed to the phenomenon of a 'catamnestic reaction' according to Max Werner (1911-1987), or to the fermentative degradation of food products. Prior to the discovery of immunoglobulin E, which marked a turning point in allergy diagnosis, and the introduction of the radioallergosorbent test in 1967, several more or less reliable techniques were used in the diagnosis of food allergy, such as pulse rate increase after food intake according to Coca, the leukopenic index, drop in basophils or drastic platelet decrease. The 'leukocytotoxic test' (Bryan's test), today called the 'ALCAT' test, shows no scientific evidence. The double-blind placebo-controlled food challenge test remains the gold standard in the diagnosis of food allergy. For the future, component-resolved diagnostics with the use of recombinant molecular allergens or chip arrays, such as the ISAC technique, hold a lot of promise. With regard to the clinical situation, a subjective selection is given, touching on the pollen-associated food allergies ('birch-mugwort-celery-spice syndrome'), as well as the new phenomenon of lethal food allergies that have appeared since the 1980s. Finally, rare ways of elicitation of a 'derivative allergy', first described by Erich Fuchs (1921-2008), for example by kissing, as well as 'oral allergy syndrome' and oral hyposensitization are considered.