Effects of recombinant human lactoferrin on calcium signaling and functional responses of human neutrophils

Abstract

Lactoferrin is a non-heme iron-binding glycoprotein with multiple health-beneficial functions including antimicrobial, antioxidant, anticarcinogenic, and immunomodulatory effects. There is emerging evidence that neutrophils may serve as targets of lactoferrin in vivo, and here we show how recombinant human lactoferrin (rhLf) can contribute to this regulation. Indeed, our results demonstrate that rhLf binds efficiently to human neutrophils and induces a variety of early cellular responses such as mobilization of intracellular Ca 2+ , remodeling of actin cytoskeleton, and degranulation (release of lysozyme and myeloperoxidase). In addition, rhLf facilitates lectin-induced H 2 O 2 production and stabilization of lectin-induced cellular aggregates. The role of calcium signaling seems to be essential for rhLf-induced activation of neutrophils, as Ca 2+ -chelators inhibit degranulation response while lectin-induced H 2 O 2 production correlates significantly with cytoplasmic Ca 2+ elevation. Taken together, our findings justify that rhLf can activate neutrophil functions in a calcium-dependent manner and hence, can potentiate innate immune responses.

Conjunctival Injection Reduction in Patients with Atopic Keratoconjunctivitis Due to Synergic Effect of Bovine Enteric-Coated Lactoferrin in 0.1% Tacrolimus Ophthalmic Suspension

“…Pastori et al had reported LF to reduce oxidative stress induced by tears of patients with keratoconus [ 20 ]. Previous studies have reported significant inter-group differences in peripheral blood lymphocyte subset ratios, neutrophils phagocytic function, and NK cell cytotoxicity [ 19 , 21 , 22 , 23 , 24 , 25 ], while the present study did not report any change in the number of eosinophils. The findings of previous studies implied that eLF administration might affect the human immune system [ 26 ], thereby reducing conjunctival injection in patients with AKC.…”

Synthesis and physicochemical characterization of zinc-lactoferrin complexes

“…However, a more important function of the LTF is the host immune response for infection or inflammation (Lambert, 2012). The wide spectrum of biological activity of LTF also includes antimicrobial (Yoshida et al, 2000), antiviral (Waarts et al, 2005), antifungal (Andersson et al, 2000), immunoregulatory, and antiinflammatory properties (Grigorieva et al, 2019). Additionally, LTF plays a role in cell proliferation and migration; among others, topical administration of bLTF enhances wound closure (Takayama, 2012).…”

Discovery of Lactoferrin as a Stimulant for hADSC-Derived EV Secretion and Proof of Enhancement of Resulting EVs through Skin Model

“…In this study, we confirmed for the first time that hLF induces a change in intracellular Ca 2+ levels in hADSCs and thereby increases hADSC-derived EV biogenesis. A recent study investigated the alteration of neutrophil calcium levels by using hLF in media containing Ca 2+ [29]. According to the authors, the addition of hLF to neutrophils resulted in transient calcium channel activation via tyrosine kinase and phospholipase C, and the activation of calcium channels by hLF was confirmed to be enhanced by the addition of CaCl 2 .…”

“…Therefore, hLF is used as a factor in human stem cell culture to increase the survival rate of stem cells via Fe 3+ ion transfer. Secondly, it has recently been confirmed that hLF is involved in the activation of Ca 2+ channels in human neurons and human neutrophils [28,29], which suggests that it may potentially enhance EV biogenesis from human stem cells. Finally, hLF is known to be effective in enhancing cell proliferation and ECM synthesis in target human cells [27,30,31].…”