Calgranulins may contribute vascular protection in atherogenesis.

摘要: Abstract S100A8, S100A9 and S100A12 are considered proinflammatory mediators of atherosclerosis. Known as calgranulins, they major components neutrophils upregulated in macrophages foam cells. They influence leukocyte recruitment, may propagate inflammation by binding TLR4 and/or receptor for advanced glycation endproducts (RAGE). However, the receptors calgranulins remain an enigma; we have no evidence or RAGE activation S100A8 S100A12. Moreover, gene regulation studies suggest antiinflammatory functions emerging reports indicate pleiotropic roles. Unlike S100A9, effectively scavenges oxidants generated myeloperoxidase system vivo, forming novel thiol modifications. is also readily S-nitrosylated, stabilizing nitric oxide transporting it to hemoglobin. S100A8-SNO reduces transmigration vasculature. S-glutathionylation modifies its effects on adhesion. Both forms inhibit mast cell activation, at least partially scavenging reactive oxygen species required signaling. Conversely, activates sequesters However suppresses cytokine induction SAA-activated monocytes macrophages, inhibits matrix metalloprotease activity. We propose that abundance types cells expressing particular microenvironments, their relative concentrations post-translational modifications distinct functional outcomes, including those protective, different stages atherogenesis.