Abstract
This review presents a summary of signalling events related to the activation of human polymorphonuclear neutrophils by a variety of soluble and particulate agonists. It is not intended as a comprehensive review of this vast field or as a presentation of the multiple new aspects of neutrophil functions that are being documented at an ever faster rate. Its aim is rather to focus on multiple aspects of major signalling pathways that, in the view of this reviewer, are currently shadowed by present trends and to provide the core evidence for their implication and the limitations of our present knowledge. More specifically, this review starts with cell surface receptors and some of their functional and biological properties and then moves on to downstream transducers (G proteins) and effectors (the phosphoinositide, tyrosine kinases, and cyclic nucleotide pathways). Classical second messengers (calcium, protein kinase C, polyphosphoinositides, and cyclic nucleotides) are emphasized. It is hoped that this presentation will not only remind present-day investigators of the central role these pathways play in the regulation of the functional responsiveness of neutrophils, but that it will also highlight some of the areas deserving additional investigation.
Highlights
The role(s) of the polymorphonuclear neutrophil granulocyte in the immune system is rapidly evolving and expanding [1]
Evidence for the phenotypic plasticity of the neutrophil as well as its functional diversity is rapidly accumulating [3]. This includes the realization that neutrophils can acquire the capacity to present antigens through the expression of MHC class II molecules [4, 5], to express functional elements of the T cell receptor [6], and to produce and secrete various cytokines and chemokines [7] that direct the differentiation and function of dendritic cells and T and B lymphocytes, that is, the effector arm of the immune system [1, 8]
The emphasis in this review will be on several aspects of signalling which have, to some extent, been relatively in the shadow recently with the recent emphasis on novel neutrophil functions [1]
Summary
The role(s) of the polymorphonuclear neutrophil granulocyte (neutrophil) in the immune system is (are) rapidly evolving and expanding [1]. Evidence for the phenotypic plasticity of the neutrophil as well as its functional diversity is rapidly accumulating [3]. This includes the realization that neutrophils can acquire the capacity to present antigens through the expression of MHC class II molecules [4, 5], to express functional elements of the T cell receptor [6], and to produce and secrete various cytokines and chemokines [7] that direct the differentiation and function of dendritic cells and T and B lymphocytes, that is, the effector arm of the immune system [1, 8]. It is intended to complement the information in the multiple excellent reviews on neutrophil signalling and functions (signalling: [9,10,11] and function: [8, 12,13,14,15,16,17,18,19,20]) that have recently been published
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