Lactoferrin in a Context of Inflammation-Induced Pathology

Abstract

Much progress has been achieved to elucidate the function of lactoferrin (LTF), an iron-binding glycoprotein, in the milieu of immune functionality. This review represents a unique examination of LTF toward its importance in physiologic homeostasis as related to development of disease-associated pathology. The immunomodulatory nature of this protein derives from its unique ability to “sense” the immune activation status of an organism and act accordingly. Underlying mechanisms are proposed whereby LTF controls disease states, thereby pinpointing regions of entry for LTF in maintenance of various physiological pathways to limit the magnitude of tissue damage. LTF is examined as a first line mediator in immune defense and response to pathogenic and non-pathogenic injury, as well as a molecule critical for control of oxidative cell function. Mechanisms of interaction of LTF with its receptors are examined, with a focus on protective effects via regulation of enzyme activities and reactive oxygen species production, immune deviation, and prevention of cell apoptosis. Indeed, LTF serves as a critical control point in physiologic homeostasis, functioning as a sensor of immunological performance related to pathology. Specific mediation of tissue pathophysiology is described for maintenance of intestinal integrity during endotoxemia, elicited airway inflammation due to allergens, and pulmonary damage during tuberculosis. Finally, the role of LTF to alter differentiation of adaptive immune function is examined, with specific recognition of its utility as a vaccine adjuvant to control subsequent lymphocytic reactivity. Overall, it is clear that while the ability of LTF to both sequester iron and to direct reactive oxygen intermediates is a major factor in lessening damage due to excessive inflammatory responses, further effects are apparent through direct control over development of higher order immune functions that regulate pathology due to insult and injury. This culminates in attenuation of pathological damage during inflammatory injury.

Modification of lactoferrin by peroxynitrite reduces its antibacterial activity and changes protein structure

“…Specifically, LF functions as an iron transporter and serves important bacteriostatic and antiviral roles . At sites of inflammation, for example, LF sequesters Fe 3+ and prevents the formation of hydroxyl radicals via the Fenton reaction, which in turn prevents lipid peroxidation from occurring . The protein structure consists of two globular lobes (N‐ and C‐lobes) connected by a three‐turn alpha‐helix .…”

Lactoferrin’s Anti-Cancer Properties: Safety, Selectivity, and Wide Range of Action

“…Other than the direct modulation of immune response, Lf strategically acts as a potent anti-inflammatory agent by scavenging ROS, pro-oxidant agents able to both promote DNA damage and induce/sustain inflammatory disorders, drastically contributing to cancer development. Lf is able to maintain the physiological balance of ROS levels by either direct binding of free iron, one of the principal actors involved in ROS production, and regulation of key antioxidant enzymes, thus globally protecting host from ROS-mediated cell and tissue damages [192]. In this respect, a recent study by Mohammed and colleagues have shown that bLf significantly down-regulated the activity of liver antioxidant enzymes, namely catalase, glutathione peroxidase, and superoxide dismutase, along with an increase of the concentration of hepatic reduced glutathione, in a murine model of diethylnitrosamine-induced hepatocarcinogenesis.…”

Влияние Экстракта Листьев Плюща На Продукцию Антимикробных Пептидов При Остром Простом Бронхите У Детей

“…Лактоферин вважають гострофазовим білком, який функціонує як представник родини алармінів, що вивільняються з нейтрофілів після їх інфікування. Лактоферин бере участь в організації зв'язку між нейтрофілами і дендритними клітинами, стимулюючи перехід від вродженої до адаптивної імунної відповіді [18]. Лактоферин, взаємодіючи з В-лімфоцитами, сприяє антитілоутворенню [27].…”