Activation of glycoprotein VI (GPVI) and C-type lectin-like receptor-2 (CLEC-2) underlies platelet activation by diesel exhaust particles and other charged/hydrophobic ligands.

Platelets are activated by a range of stimuli that share little or no resemblance in structure to each other or to recognized ligands, including diesel exhaust particles (DEP), small peptides [4N1-1, Champs (computed helical anti-membrane proteins), LSARLAF (Leu-Ser-Ala-Arg-Leu-Ala-Phe)], proteins (histones) and large polysaccharides (fucoidan, dextran sulfate). This miscellaneous group stimulate aggregation of human and mouse platelets through the glycoprotein VI (GPVI)-FcR γ-chain complex and/or C-type lectin-like receptor-2 (CLEC-2) as shown using platelets from mice deficient in either or both of these receptors. In addition, all of these ligands stimulate tyrosine phosphorylation in GPVI/CLEC-2-double-deficient platelets, indicating that they bind to additional surface receptors, although only in the case of dextran sulfate does this lead to activation. DEP, fucoidan and dextran sulfate, but not the other agonists, activate GPVI and CLEC-2 in transfected cell lines as shown using a sensitive reporter assay confirming a direct interaction with the two receptors. We conclude that this miscellaneous group of ligands bind to multiple proteins on the cell surface including GPVI and/or CLEC-2, inducing activation. These results have pathophysiological significance in a variety of conditions that involve exposure to activating charged/hydrophobic agents.

COVID-19-related health anxieties and impact of specific interventions in patients with inflammatory bowel disease in the UK.

OBJECTIVE: Health-related concerns brought on by the COVID-19 pandemic and the impact of specific local and national interventions have not been explored in patients with inflammatory bowel disease (IBD) in the UK. We evaluated perspectives of patients with IBD on the pandemic and effectiveness of information dissemination in addressing concerns. METHODS: We prospectively conducted a survey among patients with IBD during the COVID-19 pandemic to assess concerns, information-seeking behaviours, risk perception, compliance and effect of specific interventions. RESULTS: A total of 228 patients were interviewed of whom 89% reported being concerned about the impact of COVID-19 on their health. Access to at least one IBD-specific clinical interaction during the pandemic (COVID-19 information letter from IBD team, interaction with IBD team or general practitioner, Crohn and Colitis UK website visit) was significantly associated with alleviating concerns (OR 2.66; 95% CI 1.35 to 5.24; p=0.005). Seeking health information solely through unofficial channels (search engines or social media) was less likely to ease concerns (OR 0.15; 95% CI 0.03 to 0.61; p=0.008). A quarter of patients disagreed with their assigned risk groups, with majority perceiving higher-risk profiles. This discordance was greatest in patients within the moderate-risk group and constituted immunosuppression use. Nearly 40% of patients had ongoing concerns with regard to their medications of whom a third felt their concerns were not addressed. CONCLUSION: IBD-specific clinical interactions are associated with alleviation of COVID-19 health concerns. These findings have wider implications and emphasise importance of innovative solutions that facilitate effective communication with patients without overburdening current services.