Osteopontin is increased in cystic fibrosis and can skew the functional balance between ELR-positive and ELR-negative CXC-chemokines

Abstract

High expression of osteopontin is likely part of the dysregulated inflammation seen in CF, impairing the activities of ELR-negative chemokines that both serve as innate antibiotics and recruit NK and cytotoxic T cells, instead promoting an excessive influx of neutrophils, and may thus contribute to disease progress.

Plasma Surfactant Protein-D, Matrix Metalloproteinase-7, and Osteopontin Index Distinguishes Idiopathic Pulmonary Fibrosis from Other Idiopathic Interstitial Pneumonias

“…Osteopontin is a matricellular protein produced by macrophages that induces migration, proliferation, and adhesion of fibroblasts (31,32) and has been implicated in the pathogenesis of other fibrotic disorders (33)(34)(35)(36). Osteopontin has previously been implicated in human IPF (14).…”

Osteopontin binds and modulates functions of eosinophil‐recruiting chemokines

“…Several cell surface‐expressed receptors for OPN have been identified including CD44, α9β4, α4β1, and α9β1, the latter, when expressed on neutrophils, resulting in chemotaxis . In a recent study, we found no binding of OPN to the neutrophil‐recruiting CXC chemokines GRO‐β/CXCL2, GCP‐2/CXCL6, or IL‐8/CXCL8 nor did it reduce the receptor‐activating properties of these chemokines . Furthermore, influx of neutrophils after OPN instillation was seen in noninflamed airways of mice and, in ozone‐induced lung injury, BALF neutrophils were significantly reduced in OPN deficient compared with wild‐type mice .…”

Osteopontin That Is Elevated in the Airways during COPD Impairs the Antibacterial Activity of Common Innate Antibiotics

“…P . aeruginosa releases an elastase that generates a 60 amino acid peptide (VSS60) from full-length OPN ( Fig 4A ) [ 24 ]. To investigate whether this peptide retains properties that inhibit AMPs, viable counts was performed with P .…”