IntroductionProlonged survival and activation of eosinophils are "hallmark" features of allergic diseases. 1,2 Eosinophils are also associated with host defense mechanisms in parasitic infestations, with a variety of idiopathic hypereosinophilic syndromes, and are implicated in the pathogenesis of some immunologic and malignant disorders. 3,4 Within cytoplasmic granules eosinophils store 4 types of specific cationic proteins and several cytokines. In addition, upon stimulation they can also synthesize lipid mediators and a number of cytokines and chemokines with proinflammatory, immunoregulatory, and profibrotic properties. 5 The activatory signaling pathways regulating the activities of the eosinophils have been extensively studied. [6][7][8][9][10][11] Surprisingly, the role of inhibitory signaling pathways that could restrain eosinophil activation has been scarcely examined. Recently, it has been reported that activation of human eosinophils by siglec-8, even in the presence of IL-5 or GM-CSF, the "eosinophil survival cytokines," inhibits their survival by inducing apoptosis. 12 Furthermore, Mig (CXCL9) by binding to CCR3 has been shown to block murine eosinophil chemotaxis and function. 13,14 Notably, the importance of defining new pathways that suppress eosinophil accumulation, survival, and activation has been recently bolstered by the demonstration of a critical role for eosinophils in allergicairway inflammation in 2 different eosinophil-deficient mice. 15,16 Inhibitory receptors have been characterized on cytotoxic T cells and natural killer (NK) cells and recognize diverse ligands such as major histocompatibility complex (MHC) class I molecules, adhesion molecules, or yet undefined ligands. 17,18 Two main families of inhibitory receptors exist. The immunoglobulin receptor (IgR) superfamily is characterized by V-type Ig-like domain(s) in their extracellular domain and includes receptors such as KIRs, LIRs/ILTs, siglecs, LAIR-1, gp49B1, and IRp60. The second superfamily of inhibitory receptors consists of the calciumdependent lectins such as MAFA or CD94/NKG2A. 19 Both families can be identified by a consensus amino acid sequence, the immunoreceptor tyrosine-based inhibitory motif (ITIM), which is present in the cytoplasmic domain of these molecules. The archetype ITIM sequence is composed of 6 amino acids (Ile/Val/Leu/ Ser)-X-Tyr-X-X-(Leu/Val), where X denotes any amino acid. Upon activation, these inhibitory receptors undergo tyrosine phosphorylation, often by a Src kinase, which provides a docking site for the recruitment of cytoplasmic phosphatases having a Src homology 2 (SH2) domain such as SHP-1, -2 and SHIP-1, -2. Recruitment of For personal use only. on May 10, 2018. by guest www.bloodjournal.org From SHP-1, -2 and/or SHIP-1, -2 results in upstream inhibition of cell activation before any signaling cascade has been initiated. [17][18][19] IRp60 is a non-MHC-specific inhibitory receptor belonging to the IgR superfamily. It is expressed on many cell types including T cells, NK cells, monocytes, an...

Severity of injury from caustic ingestion damages depend on the type of ingested substance, which varies depending on ethnicity. Ingestion of caustic agents by children involves specific substances according to the season, cultural and religious festivals, and ethnicity. The majority of adult cases are intentional with more serious injuries and a higher rate of complications. In our series, ingestion of acidic substances and ingestion associated with suicide attempt had the most severe consequences.

A single topical application of mitomycin significantly reduces the severity of LTS in dogs. Reapplication after 2 days does not improve results. Prospective clinical studies are warranted to assess the efficacy in humans.

Head and neck cancer patients treated by radiation commonly suffer from a devastating side effect known as dry-mouth syndrome, which results from the irreversible loss of salivary gland function via mechanisms that are not completely understood. In this study, we used a mouse model of radiationinduced salivary hypofunction to investigate the outcomes of DNA damage in the head and neck region. We demonstrate that the loss of salivary function was closely accompanied by cellular senescence, as evidenced by a persistent DNA damage response (gH2AX and 53BP1) and the expression of senescence-associated markers (SA-bgal, p19ARF, and DcR2) and secretory phenotype (SASP) factors (PAI-1 and IL6). Notably, profound apoptosis or necrosis was not observed in irradiated regions. Signs of cellular senescence were also apparent in irradiated salivary glands surgically resected from human patients who underwent radiotherapy. Importantly, using IL6 knockout mice, we found that sustained expression of IL6 in the salivary gland long after initiation of radiation-induced DNA damage was required for both senescence and hypofunction. Additionally, we demonstrate that IL6 pretreatment prevented both senescence and salivary gland hypofunction via a mechanism involving enhanced DNA damage repair. Collectively, these results indicate that cellular senescence is a fundamental mechanism driving radiation-induced damage in the salivary gland and suggest that IL6 pretreatment may represent a promising therapeutic strategy to preserve salivary gland function in head and neck cancer patients undergoing radiotherapy. Cancer Res; 76(5); 1170-80. Ó2016 AACR.

Wound healing plays a major role in the development of acquired subglottic stenosis. Pharmacologic treatment of subglottic stenosis must address both physiologic and pathologic healing processes. The relevant Pubmed and Ovid databases from 1960 to 2007 were systematically searched. Several modulating agents have been tested. Most of them were poorly investigated. Three modalities were thoroughly studied-steroids and antibiotics, mitomycin, and antireflux medications. However, there are conflicting data regarding their role in preventing and treating subglottic stenosis. Current data support to some extent the textbook suggestions of antibiotics, steroids, and antireflux treatment. As no other treatment options exist, we recommend using these modalities for pharmacologic modulation of subglottic stenosis. Mitomycin should still be considered as an unproven treatment; its use may be considered as an adjunct. V

Our results confirm the effectiveness of nonsurgical treatment of infections limited to the parapharyngeal space, at least in the pediatric population.

Our findings provide the first evidence for a complex network of paracrine and membrane interactions between MCs and Eos. The prosurvival phenotype induced by this MC-Eos interplay may be critical for sustaining chronic allergic inflammation.

Eosinophils are involved in a variety of allergic, parasitic, malignant, and idiopathic disorders by releasing a variety of factors including specific granule proteins, lipid mediators, and proinflammatory and immunoregulatory cytokines and chemokines. In addition, they interact with various cell types in the inflamed tissue. Yet, the mechanism of eosinophil activation is still poorly understood. Recently, we described the expression and function of the CD2-subfamily of receptors and especially 2B4 on human eosinophils. In this study we focus on CD48, the high-affinity ligand of 2B4. CD48 is a GPI-anchored protein involved in cellular activation, costimulation, and adhesion, but has not been studied on eosinophils. We demonstrate that human eosinophils from atopic asthmatics display enhanced levels of CD48 expression and that IL-3 up-regulates CD48 expression. Furthermore, cross-linking CD48 on human eosinophils triggers release of eosinophil granule proteins. Assessment of CD48 expression in a murine model of experimental asthma revealed that CD48 is induced by allergen challenge and partially regulated by IL-3. Additionally, anti-IL-3 reduces CD48 expression and the degree of airway inflammation. Thus, CD48 is an IL-3-induced activating receptor on eosinophils, likely involved in promoting allergic inflammation.