@article {1829, title = {Mast cells are critically involved in serum-mediated vascular leakage in chronic urticaria beyond high-affinity IgE receptor stimulation.}, journal = {Allergy}, volume = {66}, year = {2011}, month = {2011 Dec}, pages = {1538-45}, abstract = {

BACKGROUND: Chronic urticaria (CU) is one of the most common skin disorders whose pathogenic mechanisms are not fully clarified. Autoimmune aetiology can be ascribed to 45\% of patients with CU, and basophil histamine release is positive in 40\% of cases. Our aim was to use a novel approach to evaluate the serum permeabilizing effect to identify the mediators of endothelial cell (EC) leakage and to define the role of mast cells (MCs) in the process.

METHODS: Permeabilizing activity of sera from 19 patients with CU and 11 healthy blood donors was evaluated by measuring serum-induced degranulation of two MC lines, expressing (LAD2) or lacking (HMC-1) the IgE receptor. Mast cell supernatant (SN) was then incubated with an EC monolayer, and endothelial permeability was evaluated by Fluorescein isothiocyanate-bovine serum albumin leakage in a transwell system.

RESULTS: All 19 patient sera failed to induce direct EC leakage, but 15/19 and 17/19 promoted degranulation of HMC-1 and LAD2, respectively. Interestingly, 85\% of autologous serum skin test-negative sera were able to cause MC degranulation. Also, 17/19 SNs from HMC-1 and all SNs from LAD2 incubated with CU sera increased endothelial permeability. Endothelial cell leakage remained unchanged after Ig depletion and was prevented by antihistamine, platelet-activating factor or leukotriene antagonist.

CONCLUSIONS: Our study shows that CU sera are able to degranulate MCs through an IgE- and IgG-independent mechanism. The nature of histamine-releasing factors involved is still unclear, but our finding opens new ways to the understanding of the pathogenesis of CU, particularly in patients not showing circulating autoantibodies to FcεRI or IgE.

}, keywords = {Adult, Aged, Capillary Permeability, Chronic Disease, Endothelial Cells, Female, Histamine Release, Humans, Male, Mast Cells, Middle Aged, Receptors, IgE, Serum, Urticaria, Young Adult}, issn = {1398-9995}, doi = {10.1111/j.1398-9995.2011.02704.x}, author = {Bossi, F and Frossi, B and Radillo, O and Cugno, M and Tedeschi, A and Riboldi, P and Asero, R and Tedesco, F and Pucillo, C} } @article {1630, title = {Mannose-binding lectin is produced by vaginal epithelial cells and its level in the vaginal fluid is influenced by progesterone.}, journal = {Mol Immunol}, volume = {48}, year = {2010}, month = {2010 Nov-Dec}, pages = {281-6}, abstract = {

Mannose-binding lectin (MBL) is a recognition molecule of the complement (C) system and binds to carbohydrate ligands present on a wide range of pathogenic bacteria, viruses, fungi, and parasites. MBL has been detected in the cervico-vaginal cavity where it can provide a first-line defence against infectious agents colonizing the lower tract of the reproductive system. Analysis of the cervico-vaginal lavage (CVL) obtained from 11 normal cycling women at different phases of the menstrual cycle revealed increased levels of MBL in the secretive phase. Part of this MBL derives from the circulation as indicated by the presence of transferrin in CVL tested as a marker of vascular and tissue permeability. The local synthesis of MBL is suggested by the finding that its level is substantially higher than that of transferrin in the secretive phase. The contribution of endometrium is negligible since the MBL level did not change before and after hysterectomy. RT-PCR and in situ RT-PCR analysis showed that the vaginal tissue, and in particular the basal layer of the epithelium, is a source of MBL which binds to the basal membrane and to cells of the outer layers of the epithelium. In conclusion, we have shown that MBL detected in CVL derives both from plasma as result of transudation and from local synthesis and its level is progesterone dependent increasing in the secretive phase of the menstrual cycle.

}, keywords = {Adolescent, Adult, Body Fluids, Enzyme-Linked Immunosorbent Assay, Epithelial Cells, Female, Humans, Immunohistochemistry, Mannose-Binding Lectin, Menstrual Cycle, Progesterone, Reverse Transcriptase Polymerase Chain Reaction, Vagina, Young Adult}, issn = {1872-9142}, doi = {10.1016/j.molimm.2010.07.016}, author = {Bulla, R and De Seta, F and Radillo, O and Agostinis, C and Durigutto, P and Pellis, V and De Santo, D and Crovella, S and Tedesco, F} }