Bacterial-lipopolysaccharide-induced release of lactoferrin from human polymorphonuclear leukocytes: role of monocyte-derived tumor necrosis factor alpha

Abstract

We have examined the role played by human peripheral blood monocytes in mediating responses of human polymorphonuclear leukocytes (PMN) to bacterial lipopolysaccharide (LPS) in vitro. When incubated with Salmonella typhimurium LPS at 37°C, human PMN suspended in serum-free buffer released the specific granule constituent lactoferrin into the surrounding medium. Release of lactoferrin from PMN varied with the concentration of LPS (1 to 1,000 ng/ml) as well as with the duration of incubation (2 to 60 min) and was not accompanied by significant release of the cytoplasmic enzyme lactate dehydrogenase. LPS-induced release of lactoferrin from PMN was augmented significantly when cell suspensions were supplemented with additional monocytes and lymphocytes. Only monocytes, however, secreted significant amounts of lactoferrin-releasing activity (in a time-and concentration-dependent manner) when incubated separately with LPS. Lactoferrinreleasing activity was heat (80°C for 15 min) labile, eluted after chromatography on Sephadex G-100 with an apparent molecular weight of approximately 60,000, and was inhibited by antibodies to tumor necrosis factor a. Thus, LPS-induced noncytotoxic release of lactoferrin from human PMN suspended in serum-free buffer is mediated, at least in part, by tumor necrosis factor a derived from contaminating monocytes.

Early response in neonatal septicemia. The effect of Escherichia coli, Streptococcus agalactiae and tumor necrosis factor on the generation of lactoferrin

“…Our study confirms that TNF induces the generation of LF (13,16). In addition, TNF had a significant stimulative effect on the generation of TPL in both groups.…”

Lactoferrin release and interleukin-1, interleukin-6, and tumor necrosis factor production by human polymorphonuclear cells stimulated by various lipopolysaccharides: relationship to growth inhibition of Candida albicans

“…Lactoferrin levels in plasma are known to increase during inflammation, accompanied by a decrease in the lactoferrin content of PMN (19,45). Lactoferrin is stored in secondary granules, and several cytokines as well as LPS are able to induce its release (1,25). Further studies are needed to know whether other proteins released by PMN could potentiate and act in concert with lactoferrin in inhibiting Candida growth and whether this activity relies only on the depletion of iron in the medium.…”

“…Ability of lactoferrin itself to inhibit Candida growth and its importance in the anticandidal activity of neutrophils. Since lactoferrin acts as a bacteriostatic agent (23)(24)(25)(26)(27)(28)(29)(30)(31)(32), and, as shown by the results in the preceding sections, it was released in appreciable amounts during LPS stimulation, we examined whether lactoferrin had a direct effect on the growth of C. albicans. By the same rapid [3H]glucose uptake assay used to assay lysis of PMN, we found that this iron-binding protein was able to inhibit C. albicans growth in a dose-dependent manner over a range from 1 to 100 p,g/ml.…”

“…In particular, LPS induce a variety of responses in monocytes and polymorphonuclear cells (PMN; neutrophils) both in vitro and in vivo (5,8,22), of which some may be related to the mechanism of endotoxic shock, a severe clinical entity (29,43), as well as to other manifestations of LPS activity in the pathophysiology of infections (31,46). Among the neutrophil responses primed by endotoxin are the enhanced expression of adherence-related membrane glycoproteins (such as the CD11-CD18 family [24,38]) and secretion of oxygen metabolites, inflammatory factors, hydrolases, and lactoferrin (18,20,21,25). Increases in microbial killing and migration are also commonly observed in LPS-stimulated PMN (6,7), and augmented production of platelet activation factor and leukotrienes has been reported (14,44).…”

Toxicity of OKT3 increases with dosage: a controlled study in renal transplant recipients

“…Recently, we reported that within 15 min after the first administration of 5 mg OKT3, complement activation via the classical pathway occurred, followed by early activation of neutrophils [MI. The late and sustained activation of neutrophils contributed to the release of cytokines [5,13,17,191. As with septic shock, activation of complement and neutrophils has been considered a possible pathogenetic factor in the development of side effects following the first administration of OKT3 [ll, 12,14,20,21,25].…”