Lactoferrin, an Iron-Binbing Protein Ni Neutrophilic Leukocytes

Abstract

Lactoferrin, an iron-binding protein previously shown to occur in many external secretions, is identified as one of the major proteins present in human and guinea pig neutrophilic polymorphonuclear leukocytes. The identification of this protein in leukocyte extracts was based upon a comparison of its electrophoretic, antigenic, and iron-combining properties with the corresponding properties of the same protein isolated from human and guinea pig milk. Immunochemical quantitations showed that lactoferrin occurs in human neutrophilic leukocytes at the concentration of 3 µg per 106 cells. Tissue cultures from guinea pig bone marrow and spleen actively synthesized the protein, as shown both by net production of lactoferrin and incorporation of labeled amino acids into the protein. Immunohistochemical data indicate that lactoferrin first appears in myeloid cells at the stage of the promyelocyte.

Mechanisms of Attachment of Neutrophils to Candida albicans Pseudohyphae in the Absence of Serum, and of Subsequent Damage to Pseudohyphae by Microbicidal Processes of Neutrophils In Vitro

“…In our experiments, damage to pseudohyphae was not inhibited by concentrations of iron which were 10-fold higher than that calculated as required to saturate all neutrophil lactoferrin (36,37).…”

“…Other potential microbicidal mechanisms were then evaluated. The amount of iron required for total binding of lactoferrin was calculated from the molecular weight and known content of lactoferrin in neutrophils (36,37). 10-fold excess ferric chloride or ferric ammonium sulfate was added to incubations of neutrophils and Candida, without effect on damage to Candida (Table IV).…”

Lactoferrin and transferrin damage of the Gram-negative outer membrane is modulated by Ca2+ and Mg2+

“…The highest level of transferrin is in serum, and that of lactoferrin within polymorphonuclear leucocytes and in mucosal fluids (Masson et al, 1966(Masson et al, , 1969. They have protean effects on micro-organisms ; variably acting as growth factors, inducing iron uptake systems, and for selected bacteria producing bacteriostasis (Bullen, 198 1 ;Bullen et al, 1978;Griffiths, 1975;Norrod & Williams, 1978).…”

Iron in Infection and Immunity

“…Mucosal secretions contain high concentrations of lactoferrin, comprising a constitutive mechanism for iron limitation at mucosal surfaces. Additionally, the specific ("secondary") granules of neutrophils contain lactoferrin, which is released at infectious sites in response to cytokines (Masson et al, 1969). Moreover, unlike transferrin, lactoferrin maintains iron-binding capacity at low pH and therefore may be a more effective scavenger in acidotic infectious foci (Baker and Baker, 2012).…”