Chronic Allergy Research Articles

IgE- and IgE+Ag-mediated mast cell migration in an autocrine/paracrine fashion

AbstractMast cells are the major effector cells for immediate hypersensitivity and chronic allergic reactions. These cells accumulate in mucosal tissues of allergic reactions, where immunoglobulin E (IgE) is produced locally. Here we provide evidence that, in addition to antigen that can attract IgE-bound mast cells, the type of IgE molecules that efficiently activate mast cells can promote the migration of mast cells in the absence of antigen. IgE- and IgE+Ag-mediated migration involves an autocrine/paracrine secretion of soluble factors including adenosine, leukotriene B4, and several chemokines. Their secretion depends on 2 tyrosine kinases, Lyn and Syk, and they are agonists of G-protein-coupled receptors and signal through phosphatidylinositol 3-kinase γ, leading to mast cell migration. In mouse experiments, naive mast cells are attracted to IgE, and IgE-sensitized mast cells are attracted to antigen. Therefore, IgE and antigen are implicated in mast cell accumulation at allergic tissue sites with local high IgE levels. (Blood. 2005;105:3222-3229)

Allergic fungal sinusitis presenting as visual loss and facial dysmorphia in New York City

RATIONALE: Allergic fungal sinusitis (AFS) is a chronic allergic reaction to ubiquitous fungi which causes thick mucoid accumulation in the sinuses. AFS is commonly diagnosed in humid regions such as the southeastern and southwestern United States. AFS occurs in immunocompetent young atopic adults with nasal polyps and persistent sinusitis, despite adequate medical/surgical treatment. The diagnosis requires fungal elements in allergic mucin without tissue invasion. Most patients have elevated total and fungal specific IgE levels.

Physiological Mechanisms of Histamine-Induced Hyposensibilization in Infectious Allergic Bronchial Asthma

Ascendancy therapy with histamine had a distinct clinical effect and caused stable remission in patients with infectious allergic bronchial asthma. Therapy normalized not only histamine release but also the balance of all components of the immune system. Beginning from minimum doses of histamine, gradual adaptation of the immune system was observed and normalized the immune response. To improve the clinical efficiency, it is important to control the increase of the prescribed doses of histamine. A simple test for a change in granulocyte migration to the oral cavity was proposed for this purpose. The paper discusses the probability that common mechanisms underlie immunotherapy in specific chronic allergy, ascendancy therapy with histamine in intrinsic allergy, and dosed immunotherapy in chronic inflammatory disorders.

A model of chronic IgE-mediated food allergy in ovalbumin-sensitized mice.

Food allergy is most frequently the result of IgE-mediated hypersensitivity reactions. Here, we describe a chronic model in which some of the intestinal and systemic consequences of continuous egg white solution ingestion by ovalbumin-sensitized eight-week-old BALB/c mice, 6 animals per group, of both sexes, were investigated. There was a 20% loss of body weight that began one week after antigen exposure and persisted throughout the experiment (3 weeks). The sensitization procedure induced the production of anti-ovalbumin IgG1 and IgE, which were enhanced by oral antigen exposure (129% for IgG1 and 164% for IgE, compared to sensitization values). Intestinal changes were determined by jejunum edema at 6 h (45% Evans blue extravasation) and by a significant eosinophil infiltration with a peak at 48 h. By day 21 of continuous antigen exposure, histological findings were mild, with mast cell hyperplasia (100%) and increased mucus production (483%). Altogether, our data clearly demonstrate that, although immune stimulation was persistently occurring in response to continuous oral antigen exposure, regulatory mechanisms were occurring in the intestinal mucosa, preventing overt pathology. The experimental model described here reproduces the clinical and pathological changes of mild chronic food allergy and may be useful for mechanistic studies of this common clinical condition.

Histamine H4 antagonism: a therapy for chronic allergy?

Chronic inflammatory diseases such as bronchial asthma, allergic gastrointestinal disease, and atopic dermatitis are characterized by the selective recruitment and activation of distinct subtypes of leukocytes, particularly eosinophils, into the tissue from peripheral blood (Rothenberg, 1998). Eosinophils, along with mast cells, are postulated to play a key role in the pathophysiology of these chronic diseases. The striking accumulation of eosinophils in allergic disease has stimulated intense scientific examination leading to the discovery of numerous molecular mechanisms responsible for this process. Eosinophils, like all leukocytes, migrate from the vascular lumen, across the endothelial cell surface into the appropriate tissue sites. This elaborate mechanism, known as transendothelial migration, has been shown to be a highly orchestrated process (Springer, 1994). The migratory pathway, or chemotaxis, of the leukocyte is directly influenced by soluble molecules known as chemoattractants. These molecules reside along a tissue gradient, and bind to and activate G-protein coupled receptors (GPCRs) on the leukocyte cell surface. Several eosinophil chemoattractants have been extensively studied. Some of these molecules, the classical chemoattractants, include the complement cleavage fragments, leukotrienes and platelet-activating factor (PAF). These chemoattractants have been shown to stimulate the recruitment of a wide variety of leukocyte subtypes, and are therefore nonselective. In contrast, chemotactic cytokines (or chemokines) such as eotaxin-1, -2, -3, and monocyte chemoattractant protein (MCP)-4 are more selective for the recruitment of leukocytes associated with allergic inflammation, such as eosinophils, mast cells, and basophils.

Nasorespiratory function and craniofacial morphology—a review of the surgical management of the upper airway

Associations that are said to exist between the predominant respiratory mode and craniofacial morphology were explored during the past century and they are, once again, being hotly debated in numerous articles that can be found in a variety of scientific and other publications. Experimental evidence suggests that altered muscular function can influence craniofacial morphology. There have been many attempts to establish a cause-effect relationship between chronic nasal allergy, breathing pattern, and the growth and development of the craniofacial complex. The purpose of this article is to review some of the literature related to the possible cause-effect relationships between respiratory mode, craniofacial morphology, and malocclusion. In addition, this article will review several of the most common surgical procedures that are used in the management of pharyngeal airway problems.

Wheat Allergy: Clinical and Laboratory Findings

Background: Food allergy affects 6–8% of infants and wheat allergy is one of the common food allergies among children. The clinical and laboratory manifestations of wheat allergy were evaluated in this study. Methods: Thirty-two children (≤12 years old) with suspected wheat allergy were evaluated for wheat allergy. The patients underwent wheat skin prick test (SPT), measurement of wheat-specific IgE and wheat challenge test. The patients with a convincing history of anaphylaxis following ingestion of wheat or with a positive challenge test, and those with a history of immediate hypersensitivity reaction following ingestion of wheat in addition to a positive wheat SPT and/or positive wheat-specific IgE were considered wheat allergic. Then, the laboratory and clinical manifestations of their disease were studied. Results: Among patients with suspected wheat allergy, 24 patients with definite wheat allergy were identified. Anaphylaxis was a dominant clinical feature, accounting for 54.1% of acute symptoms. Chronic allergy symptoms like asthma and eczema were noted in 50% of the patients. Wheat-specific IgE was higher in patients with anaphylaxis (p < 0.02) and the risk of anaphylaxis was 14.4 times more in patients with wheat-specific IgE equal to or more than 3+. Conclusions: Anaphylaxis had occurred in a remarkable number of patients repeatedly, which demonstrates the severity of the reactions, poor knowledge of the disease and probable existence of more patients with mild reactions. Regarding the higher level of wheat-specific IgE in patients with anaphylaxis, wheat-specific IgE could be used to predict the severity of symptoms.

Stachys riederi Inhibits Mast Cell‐Mediated Acute and Chronic Allergic Reactions

The effect of aqueous extract of Stachys riederi var. japonica Miq. (Labiatae) (SRAE) on the mast cell‐mediated allergic and inflammatory reactions were investigated. SRAE inhibited systemic allergic reaction induced by compound 48/80. SRAE dose‐dependently inhibited passive cutaneous anaphylaxis (PCA) activated by anti‐dinitrophenyl (DNP) IgE. SRAE also dose‐dependently inhibited the histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti‐DNP IgE. Moreover, SRAE inhibited the secretion of tumor necrosis factor‐α (TNF‐α) and interleukin (IL)‐6 in phorbol 12‐myristate 13‐acetate (PMA) plus calcium ionophore A23187‐stimulated human mast cells (HMC‐1 cells). These results provide evidences that SRAE may be beneficial in the treatment of acute and chronic allergic diseases.

Análisis de la fiabilidad de los informes de alta en un servicio de cirugía general

ObjectiveTo evaluate the reliability of hospital discharge reports in the registration of comorbidity and complications in our general surgery department. Patients and methodA retrospective study of 50 medical records selected by systematic randomized sampling of all the discharge reports from our general surgery department from October 2002 to October 2003 was performed. We analyzed the reliability of hospital discharge reports regarding the registration of comorbidity including hypertension, diabetes, heart disease, hypercholesterolemia, chronic obstructive pulmonary disease, obesity and drug allergies. Reliability in the registration of complications was evaluated by selecting a surgical procedure (surgical procedures performed in colorectal disease) and by studying the correlation between the medical record and the hospital discharge report. Data are presented as percentages (95% CI). ResultsThe correlation for the registration of comorbidity was greater than 93% for all the selected variables.The correlation between medical records and discharge reports for the registration of complications was over 85%. ConclusionsOur results can be viewed as satisfactory, although there is room for improvement in the field of complications.

Chronic allergy to dietary ovalbumin induces lymphocyte migration to rat small intestinal mucosa that is inhibited by MAdCAM-1.

Few models have described a chronic food allergy with morphological changes in the intestinal mucosa. Here we established an ovalbumin (OVA)-induced, cell-mediated, allergic rat model and examined lymphocyte migration in the gut. Brown Norway rats were intraperitoneally sensitized to OVA and then given 10 mg OVA/day by gastric intubation for 6 wk. Lymphocyte subsets and adhesion molecules were examined immunohistochemically, and the migration of T lymphocytes to microvessels of Peyer's patches and villus mucosa was observed by using an intravital microscope. Serum OVA-specific IgG and IgE levels were increased in animals repeatedly exposed to OVA. Significant villus atrophy and increased crypt depth was accompanied by increased infiltration of T lymphocytes in the small intestinal mucosa of the group given OVA. Expression of rat mast cell protease II and of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) was also increased in these groups. The administration of anti-MAdCAM-1 antibody significantly attenuated the OVA-induced changes in the mucosal architecture and in CD4 T lymphocyte infiltration. Intravital observation demonstrated that in rats with a chronic allergy, T lymphocytes significantly accumulated in villus microvessels as well as in Peyer's patches via a MAdCAM-1-dependent process. Our model of chronic food allergy revealed that lymphocyte migration was increased with MAdCAM-1 upregulation.

Animal models of ocular allergy and their clinical correlations.

Ocular allergic diseases represent a wide spectrum of disorders, from the acute self-limited, mild form of seasonal allergic conjunctivitis to the chronic, severe, sight-threatening atopic keratoconjunctivitis. The least problematic forms are the most prevalent, and several animal models have contributed to elucidate their etiopathogenetic mechanisms and have served to test numerous anti-allergic compounds. The most severe and chronic, although less prevalent, ocular allergic problems have not benefited from a similar advance, with the subsequent lack of full understanding and a limited therapeutic armamentarium. Research in this field is currently concentrating efforts in developing more protracted models of ocular allergic inflammation involving the cornea and mimicking more closely the human disease caused by chronic ocular allergy. Most recent experimental models are demonstrating that inhibiting Th2 cells and their secreted cytokines might be one important therapeutic target for inhibiting chronic allergic inflammation in the ocular surface.

Immune regulation by regulatory T cells: implications for transplantation

The induction of antigen-specific T cell tolerance and its maintenance in the periphery are critical for the immune system to prevent autoaggressive immune responses. Our current state of knowledge about the immunoregulatory mechanisms responsible for T cell tolerance in the periphery offers new possibilities for immunomodulation to prevent transplant rejection as well as to diminish autoimmune reaction or chronic allergy. There is growing evidence that dendritic cells, besides their well-known T cell stimulatory functions, also maintain and regulate T cell tolerance in the periphery. This control function is exerted by certain maturation stages and subsets of dendritic cells, and can be further influenced and modulated by immunoregulatory cytokines and drugs. The regulatory functions of dendritic cells include the induction of T cell anergy, of T cells with regulatory properties and of T cells that produce immunosuppressive cytokines such as IL-10 or TGF-β. Additionally, distinct subsets of resident regulatory T cells generated in the thymus play a central role in maintenance of peripheral tolerance by active suppression of effector T cell populations. These CD4 +CD25 + regulatory T cells inhibit a variety of autoimmune and inflammatory diseases and they are also efficient in the suppression of alloantigen responses. This review summarises the current knowledge regarding the immunoregulatory role of dendritic cells and the functional activities of resident regulatory T cells as guardians for peripheral T cell tolerance.

Phosphoinositide 3-kinase gamma: a key modulator in inflammation and allergy.

Chronic inflammation and allergy involve the activation of tissue-resident cells and, later on, the invasion of effector cells. We have previously shown that the loss of phosphoinositide 3-kinase (PI3K) gamma impairs chemokine-dependent migration of neutrophils and macrophages both in vitro and in vivo. On the other hand, PI3K gamma is not required either during phagocytic processes or in the activation of bactericidal activities like granule secretion and particle-mediated respiratory burst in neutrophils. Tissue mast cells are key regulators in allergy and inflammation and release histamine upon clustering of their IgE receptors. We have demonstrated that murine mast cell responses are exacerbated in vitro and in vivo by autocrine signals, and require functional PI3K gamma. Adenosine, acting through the A(3) adenosine receptor, as well as other agonists of G(alpha i)-coupled receptors, transiently increased PtdIns(3,4,5) P (3) exclusively via PI3K gamma. PI3K gamma-derived PtdIns(3,4,5) P (3) was instrumental for initiation of a sustained influx of external Ca(2+) and degranulation. Mice that lacked PI3K gamma did not form oedema when challenged by passive systemic anaphylaxis. PI3K gamma thus relays inflammatory signals through various GPCRs, and is thus central to mast cell function. Taken together, this suggests that pharmaceutical targeting of PI3K gamma might alleviate inflammation at both early and late stages of the allergic response.

Vaccinology: past achievements, present roadblocks and future promises

Of all the branches of modern medicine, vaccinology can claim to be the one that has contributed most to the relief of human misery and the spectacular increase in life expectancy in the last two centuries. It is the only science that has eradicated an infectious disease—smallpox—responsible for 8–20% of all deaths in several European countries in the 18th century. Other disabling and lethal diseases, like poliomyelitis and measles, are targeted for eradication. Currently, it is estimated that immunization saves the lives of 3 million children a year but 2 million more lives could be saved by existing vaccines. The success of vaccines in controlling and eliminating diseases has, paradoxically, been the cause of a revival of the anti-vaccination movement which in the absence, in developed countries, of many erstwhile common infectious diseases such as diphtheria, tetanus, polio, pertussis, measles, rubella and mumps has come to believe that vaccination is not only no longer necessary but is even dangerous. This is because it accepts, as “reactions”, any untoward health event that occurs after administration of a vaccine. Most vaccine “reactions”, therefore, appear to be more frequent than vaccine-preventable diseases. Public Health Authorities, aware of the great value of vaccines to society, are facing an uphill battle to get them accepted by a growing proportion of so-called educated minorities, thus endangering disease elimination. Other developments, in the last two decades, that have hampered vaccine usage have been the exploding costs of research, development and manufacture of new vaccines and the emphasis still placed on therapy in preference to prevention in medicine. This has led to the erroneous perception that vaccines are expensive although they are, in most cases, more cost-effective than the popular wait-see-treat approach. A favorable trend for vaccinology has been fuelled by recent major breakthroughs in the sciences of immunology, molecular biology, genomics, proteomics, physico-chemistry and computers that promise a bright future for prevention, not only of acute infectious diseases, but also treatment of conditions like chronic infections, allergy, auto-immune diseases and cancer where some malfunctioning of the immune system is thought to play a part. Vaccines are being made more user-friendly by the development of combined vaccines and less painful and invasive inoculation techniques than the traditional syringe and needle. Recent new initiatives, like the Global Alliance on Vaccines and Immunization (GAVI),which are gathering new sources of funding for vaccination, should be beneficial for vaccinology.

Proteomic analysis of human eosinophil activation mediated by mast cells, granulocyte macrophage colony stimulating factor and tumor necrosis factor alpha.

We assessed mast cell influence on eosinophils, the prominent cells in late and chronic allergic reactions, by comparing the proteomic pattern of eosinophils incubated with mast cells, tumor necrosis factor alpha (TNF-alpha) or granulocyte macrophage colony stimulating factor (GM-CSF). Eosinophils were incubated with the human mast cell line HMC-1 cellular sonicate and their survival and GM-CSF production were evaluated. For proteomic studies, eosinophils were cultured with HMC-1 sonicate, TNF-alpha or GM-CSF in the presence of [(35)S]methionine, solubilized and submitted to isolelectric focusing separation and sodium dodecyl sulfate polyacrylamide gel electrophoresis in the ISODALT system, followed by radiofluorography and computer image analysis. HMC-1-incubated eosinophils displayed increased survival partly mediated by mast cell-associated TNF-alpha, and produced GM-CSF. Metabolically labeled eosinophils incubated with either HMC-1, TNF-alpha or GM-CSF released eosinophil peroxidase. Comparison of two-dimensional gel spots from the eosinophils revealed that each of the three activating signals yielded a distinctly different proteomic pattern of labeled polypeptides. GM-CSF provided the strongest signal and the highest rate of protein synthesis (1,018 spots) followed by TNF-alpha (747 spots) and HMC-1 sonicate (611 spots). A portion of spots differed both in terms of quality and quantity. Although each stimulus induced similar functional effects, the resulting biosynthetic programs of the eosinophils greatly differed. The presented proteomic analysis is the first step in the exploration of molecular mechanisms involved in eosinophil activation.

피하기종을 동반한 재발성 기이하선염

Recurrent swelling of one or both parotid glands is relatively frequent in children. The most common cause is a mumps viral infection. Other causes of this condition include non-mumps viral infection, acute and chronic bacterial infection, allergic or drug reaction, metabolic or systemic disorders, trauma, neoplasm, and ductal obstruction and pneumopatotitis. Pneumoparotitis is a condition of air insufflation into the acini of the parotid gland via Stensen’s duct. The air insufflation may rupture the parotid capsule, and spread into the subcutaneous tissues of the face and neck. It may even cause pneumomediastinum. Self-induced autoinsufflation is the most common cause of pneumopatotitis in children and adolecents. We present a case of a 11-year-old boy with history of recurrent swelling of both parotid glands with subcutaneous emphysema. The clinical presentation of pneumoparotitis with subcutaneous emphysema, its pathophysiology, diagnosis, and management are discussed and a review of literature is presented. (J Clinical Otolaryngol 2002;13:238-241)

High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis.

Women with endometriosis may also have associated disorders related to autoimmune dysregulation or pain. This study examined whether the prevalence of autoimmune, chronic pain and fatigue and atopic disorders is higher in women with endometriosis than in the general female population. A cross-sectional survey was conducted in 1998 by the Endometriosis Association of 3680 USA members with surgically diagnosed endometriosis. Almost all responders had pain (99%), and many reported infertility (41%). Compared with published rates in the general USA female population, women with endometriosis had higher rates of hypothyroidism (9.6 versus 1.5%, P < 0.0001), fibromyalgia (5.9 versus 3.4%, P < 0.0001), chronic fatigue syndrome (4.6 versus 0.03%, P < 0.0001), rheumatoid arthritis (1.8 versus 1.2%, P = 0.001), systemic lupus erythematosus (0.8 versus 0.04%, P < 0.0001), Sjögren's syndrome (0.6 versus 0.03%, P < 0.0001) and multiple sclerosis (0.5 versus 0.07%, P < 0.0001), but not hyperthyroidism or diabetes. Allergies and asthma were more common among women with endometriosis alone (61%, P < 0.001 and 12%, P < 0.001 respectively) and highest in those with fibromyalgia or chronic fatigue syndrome (88%, P < 0.001 and 25%, P < 0.001 respectively) than in the USA female population (18%, P < 0.001 and 5%, P < 0.001 respectively). Hypothyroidism, fibromyalgia, chronic fatigue syndrome, autoimmune diseases, allergies and asthma are all significantly more common in women with endometriosis than in women in the general USA population.

Antiallergic tea catechin, (-)-epigallocatechin-3-O-(3-O-methyl)-gallate, suppresses FcepsilonRI expression in human basophilic KU812 cells.

We previously found that the O-methylated derivative of (-)-epigallocatechin-3-O-gallate (EGCg), (-)-epigallocatechin-3-O-(3-O-methyl)-gallate (EGCG' '3Me), has potent antiallergic activity. The high-affinity IgE receptor, FcepsilonRI, is found at high levels on basophils and mast cells and plays a key role in a series of acute and chronic human allergic reactions. To understand the mechanism of action for the antiallergic EGCG' '3Me, the effect of EGCG' '3Me on the cell surface expression of FcepsilonRI in human basophilic KU812 cells was examined. Flow cytometric analysis showed that EGCG' '3Me was able to decrease the cell surface expression of FcepsilonRI. Moreover, immunoblot analysis revealed that total cellular expression of the FcepsilonRI alpha chain decreased upon treatment with EGCG' '3Me. FcepsilonRI is a tetrameric structure comprising one alpha chain, one beta chain, and two gamma chains. The level of mRNA production of each subunit in KU812 cells was investigated. EGCG' '3Me reduced FcepsilonRI alpha and gamma mRNA levels. The cross-linkage of FcepsilonRI causes the activation of basophils, which leads to the secretion of inflammatory mediators including histamine. EGCG' '3Me treatment inhibited the FcepsilonRI cross-linking-induced histamine release. These results suggested that EGCG' '3Me can negatively regulate basophil activation through the suppression of FcepsilonRI expression.

T-cell tolerance in allergic response.

Allergic diseases are immunological disorders (1), which originate from the activation of T-cell subsets secreting allergic, inflammatory factors including interleukin (IL)-4 and IL-5 and/or IL-13. The regulation of allergen-specific T cells is one of the strategies to control disease. However, available drugs such as steroids are not allergen-specific and only temporarily suppress the activity of immune cells. Thus, they are not curative and accompanied by side effects. In contrast, allergen-specific immunotherapy (SIT) can specifically restore normal immunity against allergens. Successful SIT is characterized by the induction of peripheral T-cell tolerance against the allergen (2, 3). Although successful SIT applies predominantly for treatment of monoor oligo-specific allergies, the underlying immuno-regulatory mechanism can possibly be projected on allergic disease in general. Lymphocyte tolerance describes a complex process, which balances the reactivity against foreign vs. autologous antigens. Autoreactive lymphocytes are eliminated early in their thymic development, a process, which is covered by the term central tolerance (4). T cells, however, might escape thymic selection or might face harmless antigens later in their development, which are meant to be under the control of peripheral tolerance (5). Lymphocyte tolerance is likely to be a dynamic process (6), which adapts to the development of the organism to effectively distinguish autologous from foreign antigens. Recent investigations on peripheral tolerance revealed several basic mechanisms. These mechanisms comprise cell survival, as cells might undergo apoptosis, which would delete antigen specificities. Furthermore, antigens located in anatomically ‘hidden’ areas could be neglected by the immune system. Finally, cells could be suppressed and/or undergo clonal anergy, which keeps already existing lymphocyte specificities under control (7–9). The latter mechanism appears to be particularly interesting for the understanding of the pathogenesis of allergic disease, because allergenspecific T cells can be isolated, even from donors, who do not suffer from allergies. Moreover, it is frequently observed that patients are sensitized against two allergens but only show clinical symptoms against one of them. Interestingly, both the clinically silent and the pathogenic T-cell specificities, express both Th2-like cytokines.

Unlocking the secrets of galectins: a challenge at the frontier of glyco-immunology

Over the last decade, we have witnessed an explosion of information regarding the function of glycoconjugates, carbohydrate-binding proteins, and the elucidation of the sugar code. This progress has yielded not only important insights into fundamental areas of glycobiology but has also influenced other fields such as immunology and molecular medicine. A family of galactoside-binding proteins, called galectins, has emerged recently as a novel kind of bioactive molecules with powerful, immunoregulatory functions. Different members of this family have been shown to modulate positively or negatively multiple steps of the inflammatory response, such as cell-matrix interactions, cell trafficking, cell survival, cell-growth regulation, chemotaxis, and proinflammatory cytokine secretion. To introduce a comprehensive overview of these new advances, here we will explore the molecular mechanisms and biochemical pathways involved in these functions. We will also examine the role of these proteins in the modulation of different pathological processes, such as chronic inflammation, autoimmunity, infection, allergic reactions, and tumor spreading. Understanding the intimate mechanisms involved in galectin functions will help to delineate selective and novel strategies for disease intervention and diagnosis.