Lactoferrin inducible monocyte cytotoxicity defective in esterase deficient monocytes

Abstract

We recently demonstrated a higher incidence of monocyte esterase deficiency in patients with lymphoproliferative neoplasia and gastrointestinal carcinoma than in the normal population. Using lactoferrin to stimulate monocyte cytotoxicity we have now compared the abilities of esterase positive and esterase deficient monocytes to lyse K562 cells. The esterase deficient monocytes were from normal subjects whose monocytes have consistently failed to show cytochemical esterase staining over 30-72 months and which lack specific monocyte isoenzymes. The esterase positive monocytes were from age and sex matched control subjects. Esterase positive monocytes responded to lactoferrin stimulation by a five-fold increase in cytotoxicity whereas deficient monocytes failed to produce any response. These results indicate a possible defect in cytotoxicity of esterase deficient monocytes and together with the epidemiological findings suggest a link between monocyte esterase deficiency and neoplasia.

Carboxylesterase 1 (Ces1): from monocyte marker to major player

“…Inhibition of Ces1 by OPs was shown to be associated with diminished tumour cell killing by monocytes 13. Constitutional deficiency of the enzyme monocyte esterase/Ces1 deficiency (MED) was shown to be associated with diminished ability to lyse K562 cells 14. Low α-naphthyl butyrate esterase activity has been reported in macrophages matured in vitro from peripheral blood monocytes of patients with non-Hodgkin lymphoma.…”

In situ Detection of Human Monocyte/ Macrophage Serine Esterase-1 mRNA Expression in Human Tissues

“…Many attempts have been made to clarify the physiological function of monocyte serine esterase. Proteolytic properties have been investigated [20], and participation in detoxification and cytotoxicity against tumor cells has been proposed [7][8][9]17]. The latter function is based on the observations that inherited and acquired deficiency in monocyte serine esterase is associated with decreased cytotoxicity in vitro and that a lack of monocyte serine esterase activity can be observed in patients suffering from gastrointestinal cancer and malignant lymphomas [9].…”

“…These enzyme variants were also found in monocytederived macrophages and neoplastic derivatives of the monocyte/macrophage system [3][4][5][6]. Beside detoxification, cytotoxic properties have also been proposed for this enzyme [7][8][9], but the physiological function still remains obscure.…”

Cancer prevention by bovine lactoferrin: from animal studies to human trial

“…The whey fraction is composed of five major proteins: a-lactalbumin, b-lactoglobulin, immunoglobulin, bovine serum albumin and lactoferrin. At the time the study was published, it was known that lactoferrin was present in the specific granules of neutrophils (Cramer et al 1985), and that it stimulated neutrophil motility and superoxide production, activated NK cells, and strongly augmented LAK cell activity and macrophage cytotoxicity (Gahr et al 1991;McCormick et al 1991;Nishiya and Horwitz 1982;Shau et al 1992). A year before McIntosh et al published their results, another group demonstrated that intraperitoneal injection of human LF inhibited the growth of solid tumors and the development of experimental metastases in mice (Bezault et al 1994).…”