Tinker, tailor, soldier, cell: the role of C-type lectins in the defense and promotion of disease

C-type lectins (CTLs) represent a large family of soluble and membrane-bound proteins which bind calcium dependently via carbohydrate recognition domains (CRDs) to glycan residues presented on the surface of a variety of pathogens. The deconvolution of a cell's glycan code by CTLs underpins several important physiological processes in mammals such as pathogen neutralization and opsonization, leukocyte trafficking, and the inflammatory response. However, as our knowledge of CTLs has developed it has become apparent that the role of this innate immune family of proteins can be double-edged, where some pathogens have developed approaches to subvert and exploit CTL interactions to promote infection and sustain the pathological state. Equally, CTL interactions with host glycoproteins can contribute to inflammatory diseases such as arthritis and cancer whereby, in certain contexts, they exacerbate inflammation and drive malignant progression. This review discusses the 'dual agent' roles of some of the major mammalian CTLs in both resolving and promoting infection, inflammation and inflammatory disease and highlights opportunities and emerging approaches for their therapeutic modulation.

The effect of mesenchymal stem cell use on intra-abdominal adhesions in a rat model

PURPOSE: Intra-abdominal adhesions (IAA) are among the most frequently seen pathologies in general surgery practice with an increased morbidity and mortality. In the present study, we investigated the effect of locally applied mesenchymal stem cells (MSCs) on IAA. METHODS: Twenty-four Wistar Albino rats were used in the study. The rats were divided into three groups including: Sham, control, and MSCs group. On day 0, cecum was reached under anesthesia in all groups, except the Sham group. Scraping with a sponge was performed until petechial bleeding occurred. The control group received no treatment. In the stem cell group, MSCs were applied topically immediately after surgery on adhesions. The rats were sacrificed on day 10 and colon tissues and blood samples were collected for macroscopic, histopathological, and biochemical analysis. RESULTS: In our study, E-selectin, P-selectin, TNF-α and IL-1 levels were statistically significantly lower in the MSC group than the control group, while the sham group has the lowest levels. In both the macroscopic and histopathological analyses (Zühlke's scale), the least amount of adhesion was observed in the Sham group. In addition, although there was less adhesion in the MSC group than the control group, the difference did not reach statistical significance. CONCLUSION: Topical MSC application immediately after surgery suppresses the inflammatory process. However it was found to be ineffective in histopathological and macroscopic examinations performed on the 10th day.

The efficacy and safety of oral propranolol in the treatment of retinopathy of prematurity / 中国新生儿科杂志

Objective To study the changes of vascular endothelial growth factor ( VEGF) and sE－Selectin in serum before and after oral propranolol therapy for retinopathy of prematurity (ROP), and to study the safety and efficacy of oral administration of propranolol in the treatment of ROP.Method Preterm infants whose gestational age ＜32 weeks and ROP Ⅱstage without plus disease were selected as the objects of our study.The infants were randomly enrolled into treatment and placebo groups in a 1∶1 allocation.The propranolol dosage was 0.25 mg/(kg· d), twice daily orally.The duration of treatment was to complete retinal vessel development or discharge , the longest oral propranolol treatment did not exceed 30 days. Result The incidence of severe ROP in the treatment group was significantly reduced (17.1%vs.37.2%, P＝0.033), and the number requiring laser treatment of the eyes was significantly reduced (3.7%vs.12.8%, P＝0.048).After 10 days of treatment, the serum sE－Selectin decreased significantly in the treatment group, it was significantly lower than that in the placebo group ( P＜0.001).There were no mortalities in the treatment group and the placebo group.The heart rate of the treatment group was lower than that of the placebo group, however, there was no significant difference between the two groups (P＞0.05).There were no significant differences in mean arterial pressure , body weight gain, and urine volume between the two groups (P＞0.05).The serum potassium level in the treatment group was significantly higher than that in the placebo group after the treatment of 20 days and 30 days, [(4.2 ±0.9) mmol/L vs.(3.8 ± 0.4) mmol/L, ( 4.4 ±0.9 ) mmol/L vs.( 3.9 ±0.4 ) mmol/L ], the differences were statistically significant (P＜0.05).However, all the children had normal serum potassium.During treatment, there was no significant differences between the two groups for the incidence of oxygen inhalation and the number of apnea in all children (P＞0.05).Conclusion Propranolol may have a certain therapeutic effect on the progression of ROP.The oral administration was relatively safe and without significant adverse effects.

Anti-inflammatory Treatments and Serum Selectin Levels in Osteoarthritis / 日本温泉気候物理医学会雑誌

<b>Background</b>: Osteoarthritis (OA) is an important rheumatic condition accompanied by synovial inflammation. Numerous leucocytes are recruited and their migration to the inflamed arthritic joints is mediated by adhesion molecules such as E-, P-, and L-selectins. We measured the serum selectin values in OA patients undergoing Mud Pack Treatment (MPT) or treated with anti-inflammatory drugs to test whether the effect of the treatments may be monitored by the level of serum selectins.<br><b>Materials and Methods</b>: 50 OA patients were randomly divided into Group A (30 patients undergoing MPT) and Group B (20 patients receving 50mg diclofenac twice daily p. o.). Blood samples were collected from both groups before and after the treatments to test serum E-, P-, and L-selectin by ELISA methods.<br><b>Results</b>: In Group B sE-selectin level showed a significant increment after the drug assumption. In Group A, a significant increment of sL-selectin after MPT was evident, while sP-selectin level did not present any significant variation.<br><b>Discussion</b>: The study indicates that MPT and diclofenac are able to influence different adhesion molecules in OA patients. The combination of these two treatments may constitute a safe and effective anti-inflammatory therapy in rheumatic diseases.

Role of adhesion molecules in neutrophil-mediated inflammation / 中国药理学通报

Adhesion molecules are involved in neutrophil-mediated inflammation. Neutropil adhesion to endothelial cell mediated by cell adhesion molecules (CAMs) is the first and critical step during the process of inflammation. Three families of CAMs play a central role in neutrophil-endothe-lial cell interactions : the selectins, the integrins, and the immunoglobulin superfamily. These different types of CAMs interact in a programmed, sequential manner to form neutrophil-endothelial cell adhesion cascade. The initial phase of inflammation, neulrophil slowing and rolling, is mediated by selectins; subsequently, firm adhesion of neu-trophils to vessel endothelial cells occurs via binding of the activated integrins and the endothelial receptors such as intercellular adhesion molecule-1 (ICAM-1); Then, neutrophils transmigrate into the tissues, this process requires chemotactic factors, integrins and PEC AM-1. Because of the important role of CAMs in the process of inflammation. Agents may be used to block the function of CAMs as a strategy of antiinflammatory therapy.