Role of osteopontin in neutrophil function

Abstract

Summary Osteopontin (OPN) is important for the function of fibroblasts, macrophages and lymphocytes during inflammation and wound healing. In recent studies of experimental colitis we demonstrated exacerbated tissue destruction in OPN‐null mice, associated with reduced tumour necrosis factor‐α expression and increased myeloperoxidase activity. The objective of this investigation therefore was to determine the importance of OPN expression in neutrophil function. Although, in contrast to macrophages, neutrophils expressed low levels of OPN with little or no association with the CD44 receptor, intraperitoneal recruitment of neutrophils in OPN‐null mice was impaired in response to sodium periodate. The importance of exogenous OPN for neutrophil recruitment was demonstrated by a robust increase in peritoneal infiltration of PMNs in response to injections of native or recombinant OPN. In vitro, OPN–/– neutrophils exhibited reduced chemokinesis and chemotaxis towards N‐formyl methionyl leucyl phenylalanine (fMLP), reflecting a reduction in migration speed and polarization. Exogenous OPN, which was chemotactic for the neutrophils, rescued the defects in polarization and migration speed of the OPN–/– neutrophils. In contrast, the defensive and cytocidal activities of OPN–/– neutrophils, measured by assays for phagocytosis, generation of reactive oxygen species, cytokine production and matrix metalloproteinase‐9, were not impaired. These studies demonstrate that, while exogenous OPN may be important for the recruitment and migration of neutrophils, expression of OPN by neutrophils is not required for their destructive capabilities.

Osteopontin: Role in immune regulation and stress responses

“…4.3). It has been reported that OPN deficiency reduces the recruitment of macrophages, neutrophils and dendritic cells Koh et al, 2007;Weiss et al, 2001). These results imply that OPN allows the expression of chemokines that may crucially influence cell recruitment during an inflammatory challenge.…”

“…The expression and localization of CD44 in neutrophils is independent of OPN, although CD44 is required for the polarization and chemotaxis of neutrophils (Alstergren et al, 2004). Koh et al (2007) have demonstrated that OPN is important for the migration of neutrophils in vitro. They have also shown OPN-null mice are impaired in their ability to recruit PMN in vivo; however, OPN does not appear to be involved in neutrophil activities such as phagocytosis, superoxide release, or the production of cytokines and proteases.…”

“…Neutrophils (the majority of PMNs) are the primary responder to exogenous and endogenous stimuli and rapidly infiltrate the injured tissue to initiate an innate host defense. OPN is a chemoattractant for neutrophils (Weiss et al, 2001;Banerjee et al, 2006;Koh et al, 2007). Activated neutrophils release proteases and cytotoxic mediators in combination with phagocytosis and respiratory bursts to eliminate invading infectious agents.…”

“…OPN is a chemoattractant for many immune cells, including neutrophils (Koh et al, 2007), dendritic cells (Weiss et al, 2001), macrophages and T cells . It has been demonstrated both in vitro and in vivo that OPN directly induces chemotaxis and also indirectly facilitates migration of these cells to other chemoattractants ).…”

Cumulative Effects of Bone and Soft Tissue Injury on Systemic Inflammation: A Pilot Study

“…Among these is osteopontin (OPN), a bioactive protein with a broad range of functions: inflammatory response, tissue and bone repair, wound healing, and tumor genesis [8,34]. Its role as a chemotactic agent and activator of neutrophils and macrophages has been previously described [20,23]. The function of OPN during posttraumatic inflammation is not fully understood.…”