The role of neutrophil secondary granules in inflamation: modulation of lympohcyte responses

Slater, KJ, 1988. The role of neutrophil secondary granules in inflamation: modulation of lympohcyte responses. PhD, Nottingham Trent University.

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Abstract

Human neutrophils, stimulated by phagocytosis of opsonized Candida guilliermondii, were found to release an inhibitor of mononuclear cell proliferation. This inhibitor partially blocked radiolabelled nucleotide incorporation into mononuclear cell cultures stimulated by mitogens Phytohaemagglutinin and Concanavalin A) or allogeneically in a three-way mixed lymphocyte culture (ICLC). The inhibitory factor was identified as the iron binding protein Lactoferrin (Lf), and a requirement for the molecule to be carrying iron was demonstrated.

Inhibition of the MLC by Lf was found to occur only when the mononuclear cells were cultured in crowded conditions by using round bottomed wells. This enforced contact was shown to enhance proliferation dramatically, and it was this additional growth that was affected by Lf. Supernatants produced by crowded cells increased the proliferation of spread cells, whilst the addition of Lf to the cultures used to produce the supernatants reduced this effect;. Thus, it appeared that Lf was affecting the production of a growth factor released in response to close cell contact.

The growth factor was subsequently identified as Interleukin 2 (IL- 2). The production of IL-2 is dependent on Interleukin 1 (IL-1). However, no IL-1 activity could be detected in MLC supernatants. Under conditions which are known to induce IL-1 secretion, namely stimulation by lipopolysaccharide (LPS), an inhibitory effect of Lf was observed. It is suggested that in the MLC, proliferation is initiated by expression of membrane bound IL-1, and that this is inhibited by Lf, thereby explaining the requirement for crowding the cells in order to obtain an effect by the iron binding protein.

LPS stimulation of mononuclear cells was found to induce rapid secretion of a factor which dramatically enhanced neutrophil chemiluminescence in response to subsequent stimulation. The evidence suggests that this is tumour necrosis factor. Inhibition of this factor by Lf was variable, with some individuals responding and others not.

The combined data indicates a negative feedback role for Lf in the control of inflammation. The effect of Lf on production of pleotropic monokines may provide an explanation for the various reported functions of the protein.

Item Type:	Thesis
Creators:	Slater, K.J.
Date:	1988
ISBN:	9781369325157
Identifiers:	Number Type PQ10290266 Other
Rights:	This copy of the thesis has been supplied on condition that anyone who consults it is understood to recognise that its copyright rests with its author and that no quotation from the thesis and no information derived from it may be published without the author's prior written consent
Divisions:	Schools > School of Science and Technology
Record created by:	Laura Ward
Date Added:	25 Jun 2021 14:02
Last Modified:	01 Nov 2023 15:41
URI:	https://irep.ntu.ac.uk/id/eprint/43242

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