Activation of conventional protein kinase C (PKC) is critical in the generation of human neutrophil extracellular traps

BACKGROUND: Activation of NADPH oxidase is required for neutrophil extracellular trap (NET) formation. Protein kinase C (PKC) is an upstream mediator of NADPH oxidase activation and thus likely to have a role in NET formation. METHODS: Pharmacological inhibitors were used to block PKC activity in neutrophils harvested from healthy donor blood. RESULTS: Pan PKC inhibition with Ro-31-8220 (p<0.001), conventional PKC inhibition with Go 6976 (p<0.001) and specific PKCβ inhibition with LY333531 (p<0.01) blocked NET formation in response to PMA. Inhibition of novel and atypical PKC had no effect. LY333531 blocked NET induction by the diacylglycerol analogue OAG (conventional PKC activator) (p<0.001). CONCLUSIONS: Conventional PKCs have a prominent role in NET formation. Furthermore PKCβ is the major isoform implicated in NET formation

Sexual Partnering and HIV Risk among Black Men Who Have Sex with Men: New York City

Black men who have sex with men (MSM) are disproportionately affected with HIV in the US. Limited event-specific data have been reported in Black MSM to help understand factors associated with increased risk of infection. Cross-sectional National HIV Behavioral Surveillance Study data from 503 MSM who reported ≥1 male sexual partner in the past year in New York City (NYC) were analyzed. Case-crossover analysis compared last protected and last unprotected anal intercourse (UAI). A total of 503 MSM were enrolled. Among 349 tested for HIV, 18% were positive. Black MSM (N = 117) were more likely to test HIV positive and not know their HIV-positive status than other racial/ethnic groups. Case-crossover analysis of 208 MSM found that men were more likely to engage in protected anal intercourse with a first time partner and with a partner of unknown HIV status. Although Black MSM were more likely to have Black male partners, they were not more likely to have UAI with those partners or to have a partner aged >40 years. In conclusion, HIV prevalence was high among Black MSM in NYC, as was lack of awareness of HIV-positive status. Having a sexual partner of same race/ethnicity or older age was not associated with having UAI among Black MSM