ObjectiveExposure to air particulate matter (PM) is associated with chronic inflammatory and autoimmune diseases. Macrophages are responsible for the regulation of chronic inflammation. However, whether PM affects macrophage polarization remains unclear. The aim of this study was to evaluate whether nontoxic concentrations of urban PM are able to prime macrophages to altered inflammatory response upon LPS challenge.MethodsWe used two forms of the urban particulate matter SRM 1648a, intact PM and PM deprived of organic compounds (PM∆C). Peritoneal murine macrophages were exposed to different concentrations of PM for 24 h and then challenged with LPS. Production of inflammatory mediators by macrophages was measured to test immunostimulatory/priming capacity of PM.ResultsParticulate matter used at non-cytotoxic concentrations induced a dose-dependent production of proinflammatory cytokines (TNF-α, IL-6, IL-12p40). By contrast, PM∆C were not able to stimulate macrophages. However, macrophages primed with both forms of PM show proinflammatory response upon LPS challenge.ConclusionsOur data indicate that exposure of macrophages to low concentrations of PM may prime the cells to hyperinflammatory response upon contact with LPS. Further studies are necessary to explain whether the exposure of patients suffering from chronic inflammatory diseases to particulate matter is responsible for the exacerbation of clinical symptoms during bacterial infections.

Objective Pseudomonas aeruginosa effectively facilitate resistance to phagocyte killing by biofilm formation. However, the cross talk between biofilm components and phagocytes is still unclear. We hypothesize that a biofilm provides a concentrated extracellular source of LPS, DNA and exopolysaccharides (EPS), which polarize neighbouring phagocytes into an adverse hyperinflammatory state of activation. Methods We measured the release of a panel of mediators produced in vitro by murine neutrophils and macrophages exposed to various biofilm components of P. aeruginosa cultures. Results We found that conditioned media from a high biofilm-producing strain of P. aeruginosa , PAR5, accumulated high concentrations of extracellular bacterial LPS, DNA and EPS by 72 h. These conditioned media induced phagocytes to release a hyperinflammatory pattern of mediators, with enhanced levels of TNF-α, IL-6, IL12p40, PGE 2 and NO. Moreover, the phagocytes also upregulated COX-2 and iNOS with no influence on the expression of arginase-1. Conclusions Phagocytes exposed to biofilm microenvironment, called by us biofilm-associated neutrophils/macrophages (BANs/BAMs), display secretory properties similar to that of N1/M1-type phagocytes. These results suggest that in vivo high concentrations of LPS and DNA, trapped in biofilm by EPS, might convert infiltrating phagocytes into cells responsible for tissue injury without direct contact with bacteria and phagocytosis.

Taurine, the most abundant free amino acid in leukocyte cytosol traps hypohalous acids (HOCl and HOBr) to produce N-chlorotaurine (taurine chloramine, NCT and N-bromotaurine (taurine bromamine, Tau-NHBr,) respectively. Both haloamines show anti-inflammatory and antimicrobial properties. However, the therapeutic applicability of Tau-NHBr is limited due to its relatively poor stability. To overcome this disadvantage, we have synthesized the stable N-bromotaurine compounds N-monobromo-2,2-dimethyltaurine (Br-612) and N-dibromo-2,2-dimethyltaurine (Br-422). The aim of this study was to compare anti-inflammatory and microbicidal properties of Br-612 and Br-422 with that of Tau-NHBr and bromamine T (BAT). We have shown that all the tested compounds show similar anti-inflammatory properties. Importantly, the stable N-bromotaurine compounds exerted even stronger microbicidal activity than Tau-NHBr. Finally, for the purpose of topical application of these compounds we have developed a carbomer-based bioadhesive solid dosage form of BAT and Br-612, featuring sustained release of the active substance.

Biofilms are consortia of microorganisms (sessile cells) that form on various surfaces including mucosal membranes or teeth. Bacterial biofilms cause many human infections such as chronic sinusitis, acne vulgaris, periodontal diseases, and chronic wounds. These infections are persistent as they show increased resistance to antibiotics and host defense system. Taurine chloramine (TauCl) and taurine bromamine (TauBr) are the physiological products of activated neutrophils, resulting from the reaction between taurine with hypochlorous acid (HOCl) and hypobromous acid (HOBr), respectively. It has been shown in vitro that taurine haloamines exert antimicrobial properties against various pathogenic bacteria. Moreover, clinical studies have shown that both haloamines are effective in the local treatment of skin and mucose infections, including biofilm-related infections. Nevertheless, it has been not tested yet whether they can kill bacteria hidden in biofilm or disrupt biofilm structure. In this study we have investigated the capacity of TauCl and TauBr to inhibit in vitro the formation of P. aeruginosa biofilm. We have also tested their ability to destroy the mature biofilm. Our results suggest that TauBr is able to inhibit in vitro the formation of P. aeruginosa biofilm but cannot destroy the mature biofilm and effectively killed hidden bacteria. In further studies, the combined effect of TauBr and DNase, one of suggested biofilm inhibitors, was tested. Together, we conclude that TauBr is a better than TauCl candidate for local therapy of biofilm-related infections. However, a combined therapy, an application of TauBr together with other anti-biofilm agents (e.g., DNase), seems to be more promising.

Recent microbiological investigations completely changed our understanding of the role of biofilm in the formation of the mucosal immune barrier and in pathogenesis of chronic inflammation of bacterial etiology. It is now clear that formation of bacterial biofilm on dental surfaces is characteristic for existence of oral microbial communities. It has also been proved that uncontrolled biofilms on dental tissues, as well as on different biomaterials (e.g. orthodontic appliances), are the main cause of dental diseases such as dental caries and periodontitis. The aim of this paper is to explain mechanisms and consequences of orthodontic biofilm formation. We will discuss current opinions on the influence of different biomaterials employed for orthodontic treatment in biofilm formation and new strategies employed in prevention and elimination of oral biofilm ("dental plaque").