Modulation of natural killer and lymphokine-activated killer cell cytotoxicity by lactoferrin

Abstract

Natural killer (NK) and lymphokine-activated killer (LAK) cell cytotoxic functions can be strongly augmented by the iron-carrier protein lactoferrin (LF). LF significantly enhances NK and LAK activities when added at the beginning of NK or LAK cytotoxicity assays. LF is effective in augmenting cytotoxic activities at concentrations as low as 0.75 microgram/ml, and higher concentrations of LF induce greater augmentation of NK and LAK. Iron does not appear to be essential for LF to increase NK and LAK, as depleting iron from LF with the chelator deferoxamine does not affect the capacity of LF to increase cytotoxicity. LF is known to have RNase enzymatic activity, and LF enhancement of NK and LAK can be blocked by RNA. However, LFs from two different sources with over 100-fold difference in RNase activity are equally effective in enhancing NK and LAK. Furthermore, purified non-LF RNase does not modulate NK or LAK activity and DNA is as effective as RNA in blocking LF augmentation of NK or LAK cytotoxicity. Therefore, the RNase activity is unlikely to be responsible for LF enhancement of the cytotoxicities. Newborn infants are known to have low NK activity and NK and LAK cells have been implicated in host defense against microbial infections. Thus, maternal milk-derived LF may have a role in boosting antimicrobial immunity in the early stages of life. In adults, LF released from neutrophils may enhance NK and LAK functions in the inflammatory process induced by microbial infections.

Lactoferrin modulation of IL-12 and IL-10 response from activated murine leukocytes

“…Lactoferrin is an integral part of the innate immune system [30] which is recognized as an immunomodulator of leukocyte populations, including neutrophils [32], peritoneal macrophages [14], natural killer cells [11,41], T cells [12], and B cells [51]. More importantly, Lactoferrin as an adjuvant is capable of enhancing the T cell mediated DTH response to a variety of antigens including Mycobacterium bovis Calmette Guerin (BCG) [27,49,50].…”

“…Lactoferrin is an integral part of the innate immune system [30], with immunomodulatory activities on leukocytes to increase phagocytic activity of neutrophils e-mail: Jeffrey.K.Actor@uth.tmc.edu. [32], enhance activation of peritoneal macrophages [14], increase natural killer cell activity [11,41], and promote maturation of T cells [12] and B cells [51]. Furthermore, Lactoferrin is capable of enhancing delayed type hypersensitivity (DTH) responses, as measured by foot pad swelling, to a variety of antigens, including sheep red blood cells (SRBC), ovalbumin (OVA), and Mycobacterium bovis Calmette Guerin (BCG) [8,49,50].…”

Dairy products and colorectal cancer. A review of possible mechanisms and epidemiological evidence

“…Lactoferrin may have other protective functions, by activating NK cells and stimulating lymphokine-activated killer (LAK) cells (Shau et al, 1992;Sekine et al, 1997). Human lactoferrin may inhibit the development of solid tumours of the colon and of metastases from a melanoma cell line in mice (Bezault et al, 1994;Yoo et al, 1997) and may reduce significantly the incidence and number of adenocarcinomas of the large intestine in rats (Sekine et al, 1997).…”

Identification of an alternative form of human lactoferrin mRNA that is expressed differentially in normal tissues and tumor-derived cell lines

“…For example, LF is associated with activation of natural killer cells (5,6), induction of colony-stimulating activity (7), activation of polymorphonuclear leukocytes and monocytes (8), regulation of granulopoiesis (9), enhancement of antibodydependent cell cytotoxicity activity (10), stimulation of lymophokine-activated killer cell activity (5), potentiation of macrophage cytotoxicity (8), and maturation of splenic B cells (11).…”