Examples of alarmins
• High-mobility group protein B1: can be released from any cell type. Proinflammatory when bound to other alarmins and PAMPs.
• S100A8/A9/A12: released by epithelial cells and phagocytes causing inflammation with increased neutrophil adhesion, migration, and release from bone marrow. Some antibacterial activity. S100A8 and S100A9 form a heterodimer called calprotectin, often measured in feces as an indication of intestinal inflammation.
• Heat-shock proteins (HSP; HSP60 and HSP70): autoantigens stimulating pathways to suppress inflammation.
• Interleukin (IL)-33: member of the IL-1 family with proinflammatory properties through binding IL-1 receptor-like 1 (ST2) that is released by various cells including epithelia, fibroblasts, endothelial cells, osteoblasts, and immune cells.
• Antimicrobial peptides (AMPs): the main AMPs are defensins, bactericidal/permeability-increasing protein permeability-increasing protein, and cathelicidins. They are secreted by epithelial cells to form a microbial shield when the physical barriers (skin and mucous membranes) become injured. The AMPs integrate into outer cell membranes of invading microbes to form pores that disrupt the microbes’ integrity. AMPs serve as chemoattractants for innate (neutrophils, DCs) and adaptive (lymphocytes) immune cells. AMPs can govern the composition of commensal microbes that colonize body surfaces. Abnormal AMP production may contribute to diseases such as psoriasis and Crohn’s disease.