Introduction to phagocyte biology

Neutrophils, monocytes and macrophages are important in the immune surveillance of microorganisms and malignant cells. All three cell types are capable of secreting a variety of chemical mediators and of phagocytosing particulate matter. Neutrophil and monocyte recruitment to sites of infection is guided by complex phenomena that involve microbial emanations, cytokines, interleukins and microenvironment modifications of the vascular endothelium. The interaction between molecules on the surface of the phagocyte (CD11b and CD62L) with those on the endothelium (intercellular adhesion molecule 1, CD62P and CD62E) is critical for the recruitment and attachment. Following adherence to endothelium and prior to vascular emigration, the phagocytes undergo a rapid cytoskeleton rearrangement, which is necessary for chemotaxis and for exertion of their phagocytic properties against microorganisms. This latter step depends on the expression of specific receptors (FcRs, CD11b, CD14, CD35) that recognise opsonised (immunoglobulin-and/or complement-coated) microorganisms and particles.

Micoorganisms are phagocytosed into phagolysosomal vacuoles, where they are subjected to strong oxygen-dependent microbicidal systems that are characterisd by the so-called NADPH-dependent respiratory burst and oxygen-independent systems including degrading enzymes, defensins (peptide antibiotics) and cathepsin G.

In addition to their beneficial role, phagocytes may also be involved in the pathogenesis of several noninfectious diseases such as acute and chronic myocardial ischaemia, idiopathic pulmonary fibrosis, emphysema, rheumatoid arthritis and certain forms of glomerulonephritis. The tissuedamaging properties arise when phagocytes are activated; this results in the upregulation of certain membrane molecules, degranulation, with release of myeloperoxidase, elastase and other proteases, and the production of reactive oxygen species, including intermediate oxygen radicals.

The evaluation of phagocyte function is important in the diagnosis of patients who present with recurrent infections, suspected chronic granulomatous disease, suspected leukocyte adhesion deficiency (LAD) 1 and 2 or immunodeficiency states.