Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions

The endogenous cellular and molecular mechanisms that control acute inflammation and its resolution are of wide interest. Using self-resolving inflammatory exudates and lipidomics, we have identified a new pathway involving biosynthesis of potent antiinflammatory and proresolving mediators from the essential fatty acid docosahexaenoic acid (DHA) by macrophages (MΦs). During the resolution of mouse peritonitis, exudates accumulated both 17-hydroxydocosahexaenoic acid, a known marker of 17S-D series resolvin (Rv) and protectin biosynthesis, and 14S-hydroxydocosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid from endogenous DHA. Addition of either DHA or 14S-hydroperoxydocosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid to activated MΦs converted these substrates to novel dihydroxy-containing products that possessed potent antiinflammatory and proresolving activity with a potency similar to resolvin E1, 5S,12R,18R-trihydroxyeicosa-6Z,8E,10E,14Z,16E-pentaenoic acid, and protectin D1, 10R,17S-dihydroxydocosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid. Stable isotope incorporation, intermediate trapping, and characterization of physical and biological properties of the products demonstrated a novel 14-lipoxygenase pathway, generating bioactive 7,14-dihydroxydocosa-4Z,8,10,12,16Z,19Z-hexaenoic acid, coined MΦ mediator in resolving inflammation (maresin), which enhances resolution. These findings suggest that maresins and this new metabolome may be involved in some of the beneficial actions of DHA and MΦs in tissue homeostasis, inflammation resolution, wound healing, and host defense

Attitudes and practices on antibiotic use and its emerging threats among Lebanese dairy veterinarians: a case study from a developing country

IntroductionThis study aimed to explore how veterinarians (vets) rationalized their prescribing decisions for antimicrobial (AM) uses, the barriers they perceived to implement proper farm management in Lebanon, and the consecutive threats that might arise concerning the emergent spread of antimicrobial resistance in animals and the population.MethodsAmid the COVID-19 pandemic, phone call interviews were conducted with 34 veterinarians working in different demographic regions across the country. Data were analyzed qualitatively using an inductive thematic analysis.Results and discussionThe majority of veterinarians called for responsible antibiotic use. The prescribing decision of veterinarians was based mainly on suspected disease from field examination, farmer’s reports via phone calls, and the ability of the farmer to cover antibiotic costs. Very few veterinarians referred to laboratory diagnosis before prescribing a specific AM due to many obstacles. This study uncovered the absence of a trust relationship between veterinarians and farmers in Lebanon. Veterinarians provided different insights into farming practices, reflecting that farmers, in general, lack proper knowledge and implementation of farm management and that they mainly treat the herd on their own, especially in light of the current unprecedented economic crisis that Lebanon has been facing in the last three years. Above all, veterinarians revealed that AM resistance in Lebanon is markedly spreading, which calls for a serious and instantaneous set of governmental policies and regulations

Finite temperature spectral-functions of strongly correlated one-dimensional electron systems

The spectral functions of tJ and tJ_{XY} models in the limit of J/t-> 0 and at finite temperatures T>>t are calculated using the spin-charge factorized wave function. We find that the Luttinger-liquid like scaling behavior for a finite system with L sites is restricted below temperatures of the order T = J/L. We also observe weight redistribution in the photoemission spectral function in the energy range t, which is much larger than the temperature.Comment: revtex, 4 pages, 3 eps figure

Lipoxin A4 stable analogs reduce allergic airway responses via mechanisms distinct from CysLT1 receptor antagonism

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154665/1/fsb2fj078653com.pd

Impaired Phagocytosis in Localized Aggressive Periodontitis: Rescue by Resolvin E1

Resolution of inflammation is an active temporally orchestrated process demonstrated by the biosynthesis of novel proresolving mediators. Dysregulation of resolution pathways may underlie prevalent human inflammatory diseases such as cardiovascular diseases and periodontitis. Localized Aggressive Periodontitis (LAP) is an early onset, rapidly progressing form of inflammatory periodontal disease. Here, we report increased surface P-selectin on circulating LAP platelets, and elevated integrin (CD18) surface expression on neutrophils and monocytes compared to healthy, asymptomatic controls. Significantly more platelet-neutrophil and platelet-monocyte aggregates were identified in circulating whole blood of LAP patients compared with asymptomatic controls. LAP whole blood generates increased pro-inflammatory LTB4 with addition of divalent cation ionophore A23187 (5 µM) and significantly less, 15-HETE, 12-HETE, 14-HDHA, and lipoxin A4. Macrophages from LAP subjects exhibit reduced phagocytosis. The pro-resolving lipid mediator, Resolvin E1 (0.1–100 nM), rescues the impaired phagocytic activity in LAP macrophages. These abnormalities suggest compromised resolution pathways, which may contribute to persistent inflammation resulting in establishment of a chronic inflammatory lesion and periodontal disease progression

Microscale arrays for the profiling of start and stop signals coordinating human-neutrophil swarming.

Neutrophil swarms protect healthy tissues by sealing off sites of infection. In the absence of swarming, microbial invasion of surrounding tissues can result in severe infections. Recent observations in animal models have shown that swarming requires rapid neutrophil responses and well-choreographed neutrophil migration patterns. However, in animal models physical access to the molecular signals coordinating neutrophil activities during swarming is limited. Here, we report the development and validation of large microscale arrays of zymosan-particle clusters for the study of human neutrophils during swarming ex vivo. We characterized the synchronized swarming of human neutrophils under the guidance of neutrophil-released chemokines, and measured the mediators released at different phases of human-neutrophil swarming against targets simulating infections. We found that the network of mediators coordinating human-neutrophil swarming includes start and stop signals, proteolytic enzymes and enzyme inhibitors, as well as modulators of activation of other immune and non-immune cells. We also show that the swarming behavior of neutrophils from patients following major trauma is deficient and gives rise to smaller swarms than those of neutrophils from healthy individuals