Corneal transplantation rejection remains an urgent problem threatening the success rate of high-risk patients. Macrophages are involved in the rejection of corneal transplants. Macrophages have M1 and M2 phenotypes, classified according their response to external stimuli. Macrophage polarization, through which these distinct forms are activated, is not only involved in the occurrence and development of inflammation, tumors, and autoimmune and other diseases, but also participates in graft rejection. This study provides an overview of the types of macrophages and mechanisms of their polarization, and review current knowledge regarding their involvement in corneal transplantation and potential therapeutic applications. Consideration of the relationship between the direction of macrophage polarization and the determination of graft survival and how it can be modified, is important for the development of novel corneal anti-rejection therapies.β1-adrenergic receptor (β1AR)-mediated transactivation of epidermal growth factor receptor (EGFR) engages downstream signaling events that impact numerous cellular processes including growth and survival. While association of these receptors has been shown to occur basally and be important for relaying transactivation-specific intracellular events, the mechanism by which they do so is unclear and elucidation of which would aid in understanding the consequence of disrupting their interaction. Using fluorescence resonance energy transfer (FRET) and immunoprecipitation (IP) analyses, we evaluated the impact of C-terminal truncations of EGFR on its ability to associate with β1AR. While loss of the last 230 amino acid C-terminal phosphotyrosine-rich domain did not disrupt the ability of EGFR to associate with β1AR, truncation of the entire intracellular domain of EGFR resulted in almost complete loss of its interaction with β1AR, suggesting that either the kinase domain or juxtamembrane domain (JMD) may be required for this association. Treatment with the EGFR antagonist gefitinib did not prevent β1AR-EGFR association, however, treatment with a palmitoylated peptide encoding the first 20 amino acids of the JMD domain (JMD-A) disrupted β1AR-EGFR association over time and prevented β1AR-mediated ERK1/2 phosphorylation, both in general and specifically in association with EGFR. Conversely, neither a mutated JMD-A peptide nor a palmitoylated peptide fragment consisting of the subsequent 18 amino acids of the JMD domain (JMD-B) were capable of doing so. Altogether, the proximal region of the JMD of EGFR is responsible for its association with β1AR, and its disruption prevents β1AR-mediated transactivation, thus providing a new tool to study the functional consequences of disrupting β1AR-EGFR downstream signaling.Tularemia, a zoonosis generally prevalent in the northern half of the globe, is caused by Francisella tularensis. Among various Francisella tularensis species, subspecies tularensis is the most pathogenic to humans causing the infection through an airborne route, abrasions in the skin, and contact with infected animals. At present no approved vaccine exists for this intracellular pathogen. Principal defensive immunity against Francisella is T-cell mediated immunity, hence, picking out significant T-cell antigens is obligatory for Francisella vaccine advancement. In the present study, an immunoproteomics approach was employed to discover T-cell antigens by infecting dendritic cells derived from monocytes with F. tularensis NCTC10857, followed by immunoaffinity isolation of MHC class I molecules and acidic elution of bound peptides. The tandem mass spectrometry technique was used to identify the sequences of the isolated peptides. Ten MHC class I restricting Francisella derived peptides were successfully identified. Top three isolated peptide sequences were modeled and used for in silico docking study to substantiate their interaction and characterize their binding potential. selleck inhibitor Virtual docking studies further confirmed a high binding affinity for top three peptides with MHC class I molecule. The outcome of this study has led to identification of the probable vaccine candidates for human studies based on T cell-antigens against Francisella.It is well established that an intravitreal needle poke or injection of buffer is protective to the retina in models of photoreceptor degeneration due to release of endogenous neurotrophic factors. Here we assess the effect of intravitreal injection of buffer in a model of closed globe trauma that causes air-blast induced indirect traumatic optic neuropathy (bITON). We injected animals 1-day after the last bITON or sham procedure and performed assessments 1-month later. Surprisingly, we detected a lower electroretinogram (ERG), greater optic nerve damage, and increased levels of pro-inflammatory cytokines in animals given an intravitreal injection. The effect was sometimes independent of bITON and sometimes exacerbated by the injury. Retina histology appeared normal, however the total number of axons in the optic nerve was lower even in uninjured animals that were injected. The number of degenerative axons was further increased in injured animals that were injected. In contrast, we detected a decrease in the ERG a wave and b wave amplitudes, but no effect on the visual evoked potential. Levels of the pro-inflammatory cytokines, IL-1α and IL-1β were elevated in the mice that received an intravitreal injection. This increase was even greater in animals that also had a bITON. This suggests that intravitreal injections may be injurious to the optic nerve particularly during the acute stage of optic nerve injury. In addition, the data suggests a role for IL-1α and IL-1β in this response.Porcine reproductive and respiratory syndrome virus (PRRSV) displays restricted tropism to porcine alveolar macrophages in nature. Meanwhile, non-porcine cell lines derived from African green monkey kidney cell lines are permissive to PRRSV, resulting in their widespread use in PRRSV research. Furthermore, genetically modified cell lines expressing receptors targeted by PRRSV have been established. We previously established porcine immortalized kidney-derived macrophages (IPKMs) that maintained typical macrophage function. In the present study, we demonstrated the advantages of IPKMs for PRRSV research. IPKMs expressed receptors for PRRSV such as CD163 and CD169. The efficiency of virus isolation from field biological samples was higher for IPKMs than for MARC-145 cells. Five different clusters of North American type PRRSV were propagated in IPKMs. Four field strains continuously produced progeny viruses during 10 continuous passages. The efficiency of virus isolation from field biological samples and continuous progeny virus production in the sequential passages using IPKMs indicated that these cells are good vessels for PRRSV research.