Chemical immunology and allergy最新文献

Semaphorins were originally identified as axon guidance molecules involved in the development of the neuronal system. However, accumulating evidences have clearly demonstrated that the semaphorin system is not restricted to the brain but supports functions of other organs. Here, we review the rapidly emerging functions of sempahorins and, in particular class 3 semaphorin, in vascular and lymphatic systems during the development, tumor angiogenesis and ischemic revascularization.

Chemokines are a family of vertebrate-specific, small-secreted molecules that were originally identified as mediators of leukocyte migration and tissue positioning during the immune response. Subsequently, chemokines were discovered to control movement also of endothelial cells and other cell types in many different contexts. The human chemokine system comprises about 50 chemokines and more than 20 receptors belonging to the seven-transmembrane receptor family. In the present chapter, we review the literature supporting a role for chemokines in angiogenesis and lymphangiogenesis. We highlight that chemokines exert both pro- and antiangiogenic roles either by acting directly on endothelial cells or by recruiting leukocytes that, in turn, secrete angiogenic mediators. This latter mode of action is possibly the most relevant in tumor angiogenesis. Finally, we explore the angiogenic properties of nonchemokine chemoattractant molecules.

Regulatory T cells (Treg cells) are crucial in mediating immune homeostasis and promoting the establishment and maintenance of peripheral tolerance. Excess body weight and obesity are typified by 'low-degree' chronic inflammation and are associated with an increased risk of atherosclerosis, diabetes, fatty liver disease, autoimmune diseases and cancer. All these pathological conditions are characterized by chronic inflammation, abnormal cytokine production, elevated acute-phase reactants, and the activation of several inflammatory signaling pathways. In this context, the discovery of the adipose tissue-derived hormone leptin has shed fundamental insights on how these processes might occur. Leptin represents a link among metabolic disorders and immune tolerance; indeed, leptin can negatively affect the generation and proliferation of Treg cells, key players in this context. Treg cells play also a central role in tumor progression; different reports have proposed that tumor microenvironment can induce the recruitment of Treg cells which can promote tumor tolerance and angiogenesis through expression of suppressive molecules, cytokines and angiogenic factors (i.e. vascular endothelial growth factor, leptin). This work aims to discuss some of the most recent advances on the relationship between angiogenesis, leptin and immune tolerance, focusing on the role of Treg cell function in this context.

Glucocorticoids are the most effective anti-inflammatory treatment for allergic diseases, and inhaled glucocorticoids have now become the first-line treatment for asthma. Glucocorticoids were discovered in the 1940s as extracts of the adrenal cortex and this was followed by the isolation of adrenocorticotropic hormone (ACTH) from pituitary gland extracts. Cortisone and ACTH were found to be very beneficial in the treatment of rheumatoid arthritis and Kendall, Reichstein and Hench received the Nobel Prize in Physiology and Medicine for this work in 1950. Bordley and colleagues first showed that ACTH was very beneficial in the treatment of allergic diseases in 1949, but the use of systemic glucocorticoids was limited by side effects. Inhaled glucocorticoids were discovered from topical steroids developed for skin inflammation and beclomethasone dipropionate was introduced in 1972, initially in low doses but later in higher doses, and became the standard treatment for persistent asthma. Subsequently, inhaled glucocorticoids were combined with long-acting β2-agonists in combination inhalers for even greater therapeutic benefit. There is now a good understanding of the molecular basis for the anti-inflammatory effects of glucocorticoids in allergic diseases. The search for even safer glucocorticoids based on the dissociation of anti-inflammatory and side effect mechanisms is currently ongoing.

In the Middle Ages little innovative medical literature came from Western Europe. The Greek-Roman tradition with the scriptures of Hippocrates and Galenos was preserved in Byzantium and then in the Middle East by Arabic medicine; it then returned to Europe in Latin translations mostly made in Italy and Spain. There were innovative developments in Arabic medicine also with regard to the history of allergy, especially with the first description of 'rose fever', which is described as very similar in symptomatology to hay fever. Under Arabic influence, the first medical university in Salerno was famous for its well-known text Tacuinum sanitatis in which a description of asthma can be found. With the beginning of renaissance new developments were also registered in Europe, with new observations and a new way of thinking.

The formation of bradykinin in plasma requires interaction of three proteins, namely coagulation factor XII (Hageman factor), prekallikrein and high-molecular-weight kininogen (HK). Prekallikrein and HK circulate as a bimolecular complex. Initiation of the cascade upon binding to negatively charged surfaces (or macromolecules) is dependent on factor XII autoactivation, conversion of prekallikrein to kallikrein, and a feedback activation of factor XII by kallikrein. The latter reaction is extremely rapid relative to factor XII autoactivation. The kallikrein then digests HK to liberate bradykinin. The natural surface appears to be vascular endothelial cells which express binding proteins for factor XII and HK, and activation can proceed along the cell surface. Recent findings demonstrate that prekallikrein has enzymatic activity separate from that of kallikrein such that it can stoichiometrically bind and cleave HK to liberate bradykinin. It is normally prevented from doing so by the plasma C1 inhibitor. Release of heat shock protein 90 (HSP-90) from endothelial cells can convert prekallikrein to kallikrein (stoichiometrically) within the prekallikrein-HK complex, even in the absence of factor XII, and the prekallikrein-HK complex can autoactivate to generate kallikrein if phosphate is the buffering ion. The effects of phosphate ion and HSP-90 are additive. Thus, an active site appears to be induced in prekallikrein by binding to HK and any of the aforementioned reactions can generate kallikrein prior to factor XII activation by autoactivation of the HK-PK complex. This brief review highlights the major discoveries made over the past 50 years which have led to our current concepts regarding the constituents and mechanisms of activation of the plasma bradykinin-forming cascade.

Over the past 25 years, the number of Medline publications dealing with angiogenesis has increased in a nonlinear fashion, reflecting the interest among basic scientists and clinicians in this field. Under physiological conditions, angiogenesis is regulated by the local balance between endogenous stimulators and inhibitors of this process. In tumor growth, there is an imbalance between endogenous stimulator and inhibitor levels, leading to an 'angiogenic switch'. Starting with the hypothesis formulated by Judah Folkman that tumor growth is angiogenesis-dependent, this area of research has a solid scientific foundation and inhibition of angiogenesis is a major area of therapeutic development for the treatment of cancer. This paper offers an account of the most relevant discoveries in this field of biomedical research.

'Asthma' is derived from the Greek root ασθμαινω, meaning 'gasp for breath'. The term originally did not define a disease, but was employed to describe respiratory symptoms of a variety of pulmonary conditions. Over the centuries, several models have been proposed to understand the pathophysiologic abnormalities of asthma. By the beginning of the 20th century, asthma was seen to be a unique illness characterized by 'spasmodic afflictions of the bronchial tubes'. Consistent with the nature of asthma as a complex disease, the models for asthma pathogenesis have become increasingly complex. Research has moved from antiquated ideas to a descriptive functional approach to one that relies on pathophysiology in cellular and molecular biology, immunology, microbiology and genetics/genomics. As more advanced technologies for measuring lung function were developed, the features of asthma were steadily unraveled and its pathophysiology clarified. Asthma was shown to be associated with transient increases in airway resistance, reductions in forced expiratory volumes and flows, hyperinflation of the lungs and increased work of breathing, as well as abnormalities in the distribution of ventilation, perfusion and arterial blood gases. Today, asthma is seen as a chronic inflammatory disease which is not yet fully understood in its pathophysiology; therefore, therapy is still on the path to becoming optimal.

Atopic dermatitis was described in 1933 but exists since antiquity. We review descriptions of a childhood skin disease compatible with our modern diagnosis of atopic dermatitis, in ancient medicine and in nineteenth century dermatology texts. We identify Hebra's prurigo and Besnier's diathetic prurigo as forerunners of atopic dermatitis, the latter being a synthesis of infantile eczema and prurigo. The pathogenic theories which link atopic dermatitis to humoralistic medicine, to digestive diseases, to allergy may have had consequences on today's reluctance to consider atopic dermatitis as a skin disorder, the treatment of which relies mainly on topicals.