Intracellular Secretory Leukoprotease Inhibitor Modulates Inositol 1,4,5-Triphosphate Generation and Exerts an Anti-Inflammatory Effect on Neutrophils of Individuals with Cystic Fibrosis and Chronic Obstructive Pulmonary Disease
Figure 9
SLPI regulates neutrophil activity by modulating IP3 production. (a); Upon neutrophil stimulation SLPI is secreted from the cell to the extracellular environment and IP3 is formed during PLC-β activation. IP3 binds to Ca2+ voltage-gated channels on calciosomes (or endoplasmic reticulum) and allows Ca2+ ions to flow from the lumen of the calciosome toward the cell interior. The presence of Ca2+ ions within the cytosol allows cytoskeletal rearrangements such as actin polymerization and talin cleavage facilitating the process of cell degranulation and chemotaxis. (b); Exogenously added rhSLPI effectively accumulates within the cell and reduces IP3 production thereby inhibiting degranulation of antimicrobial peptides and proteins and cell migration.
