Dendritikus sejt altípusok együttműködése fiziológiás és kóros állapotban = The interplay of dendritic cell subtypes in health and disease

A dendritikus sejtek (DC) az immunfolyamatok fontos irányítói, melyek alapvető szerepet játszanak a központi és perifériás tolerancia és a gyulladásos folyamatok kiváltásában, fenntartásában és szabályozásában. Kis számuk ellenére számos, fenotípus és funkció alapján eltérő alcsoportot képviselnek. Kutatási koncepciónk szerint a DC altípusok a DC készlet védelmét, a hatékony feladatmegosztást és a celluláris együttműködési lehetőségek kihasználását szolgálja. Ennek alapján a plazmacitoid DC-ek és a monocita eredetű DC-ek altípusainak aktivációban betöltött szerepét vizsgáltuk és a DC stimulációban elsődleges szerepet játszó membránhoz kötött, valamint citoplazmatikus mintázatfelismerő receptorok ligand általi aktivációját követő jelátviteli pályák együttműködésére összpontosítottunk. Eredményeink a konvencionális és plazmacitoid DC-ekben is igazolták, hogy a mintázatfelismerő receptorok (PRR) kifejeződése még a ligandum jelenlétében sem elegendő feltétele funkcionális aktivitásuknak, hanem azt a jelpályák egymást erősítő vagy gátló hatása határozza meg. Ennek megfelelően az általunk vizsgált, lokalizációjukban eltérő, de működésük alapján átfedő aktivitással rendelkező PRR-ok által kiváltott jelek egymásra hatása alapvetően meghatározza a DC-ek válaszát és így a természetes és adaptív immunválasz irányultságát, mértékét és kimenetelét. | Dendritic cells (DC) are important regulators of immune responses, which play a pivotal role in the induction, maintenance and regulation of both peripheral tolerance and inflammation. Despite their low numbers, DC involve phenotypically and functionally distinct subtypes and subsets. Based on our concept of research, DC subtypes and subsets serve the maintenance of the DC pool, support appropriate labour distribution and promotes cell-to-cell collaborations. Thus we investigated the role of plasmacytoid DC and monocyte-derived DC subsets in the activation process of these cells and focused to the cross-talk of signaling pathways triggered by the ligation of membrane integrated and cytosolic pattern recognition receptors (PRR). Our results performed with both conventional and plasmacytoid DC revealed that the expression of PRR and their ligation by specific ligand by itself is not sufficient to induce functionality, but is highly dependent on the synergistic or inhibitory interplay of the signaling cascades actually triggered. In accordance with these findings we suggest that the collaboration of signaling cascades induced by PRR with distinct cellular localizations but overlapping functions determine the cellular response of DC and subsequently the polarization, extent and outcome of the immune response

UV light induced photodegradation of liposome encapsulated fluoroquinolones: An MS study

Fluoroquinolone antibacterial agents are among the drugsmost commonly causing phototoxic side effects. The phototoxicity may be originated in formation of reactive oxygen species upon ultraviolet exposure. Researches aiming the liposomal encapsulation of fluoroquinolones, expecting an increase in their therapeutic index, enhance the importance of studies on physicochemical properties and photostability of liposomal preparations. We studied the photodegradation of ciprofloxacin, ofloxacin and lomefloxacin by mass spectrometry upon various doses of UV irradiation. Lomefloxacin, the most phototoxic fluoroquinolone among them, was encapsulated into small unilamellar and multilamellar liposomes. Impact of vesicle structure and lipid composition – the presence of unsaturated fatty acid containing dioleoylphosphatidylcholine in dipalmitoyl-phosphatidylcholine liposomes – on the lomefloxacin photolysiswas investigated; the structure of the main photoproducts was identified by mass spectrometry. It was found that the presence and type of lipids influence the ways of photodegradation process

High prevalence of peripheral arterial disease in hypertensive patients : the Evaluation of Ankle-Brachial Index in Hungarian Hypertensives screening program

Aims: Peripheral arterial disease (PAD) can be diagnosed in asymptomatic stage, measuring ankle-brachial index (ABI). Low ABI is an indicator of increased cardiovascular risk and its inclusion to traditional risk factors can improve risk prediction. The objective of the present cross-sectional part of our large-scale, multicenter, observational study was to evaluate the prevalence of PAD in a large cohort of hypertensive patients. Methods and results: A total of 21 892 hypertensive men and women (9162 men; mean age 61.45 years) were included in our prospective study in hypertension clinics. Clinical history, physical examination, and blood analysis were taken, and the ABI was measured with the Doppler method in all patients. The prevalence of PAD (ABI 1.3) was measured. In the low, moderate, high, and very high Systematic Coronary Risk Evaluation risk groups, the prevalence of low ABI was 8.1, 11.1, 16.3, and 26%, respectively. The prevalence of PAD was lower in hypertensive patients achieving their blood pressure target (9.6 vs. 16.8%; P<0.001). Conclusions: Asymptomatic PAD was highly prevalent in the studied hypertensive population. The use of ABI screening may improve cardiovascular risk prediction. Optimal blood pressure goal values in PAD patients and cardiovascular morbidity/mortality data will be evaluated after the 5-year long prospective phase of the Evaluation of Ankle-Brachial Index in Hungarian Hypertensives program