The Eosinophil Granulocyte

Like the neutrophil, the eosinophil is a bone marrow derived, blood-borne polymorphonuclear leucocyte, but unlike the neutrophil its cytoplasm stains pink on haemotoxylin/eosin staining, and electron microscopy (see fig: 1.21) shows the large angular granules that characterize this cell. Eosinophil appear to be selectively attached to tissues as the result of specific chemotaxins (e.g. IL-5 and the other chemokines RANTES and eotaxin that are separated by macrophages and T lymphocytes). Most of the granule contents are common to the neutrophil, although some agents, e.g. eosinophil peroxidase (EPO) and major basic protein (MBP), are specific for the eosinophil. Eosinophils have probably evolved to aid human host defense against parasites such as schistosomes and worms, but they are also implicated in allergic disease such as asthma. 

From the book of:

DAVIDSON’S

Principles and Practice of Medicine

Eighteenth Edition

The Macrophage

Resident tissue macrophages, e.g. Kupffer cells in the liver, alveolar macrophages in the lung, mesangial cells in the kidney, microglial cells in the brain and resident macrophages in the peritoneum and lymph nodes, derive from circulating monocytes which originate in the bone marrow. Tissue macrophages have a number of important functions (see the information box)

Some functions of Macrophages

Inflammatory Responses

·          Initiation Generation of neutrophil chemokines (e.g. IL-8) Generation of monocyte chemokines (e.g. MIP-1α) Generation of agents (e.g. IL-1, TNF-α) that activate endothelial cells Generation of acute phase response (IL-1, TNF, IL-6) ·          Amplification Secretion of agents that stimulate bone marrow generation of leucocyte (IL-1, TNF- α) ·          Resolution Scavenging of necrotic and apoptotic cells and debris ·          Repair/ Fibrosis Remodeling – elastase, collagenase Scar formation – IL-1, platelet-derived growth factor (PDGF), fibroblast growth factor (FGF)

Immune Response

·          Antigen presentation – lymphocyte activation

Host Defense

·          Phagocytosis and killing of microorganisms by oxygen radicals, nitric oxide-dependent mechanisms and enzymes

Antitumour effects

·          Lysis of tumor cells by TNF- α and nitric oxide-dependent mechanisms

and via a range of surface receptors are able to respond in different ways to a wide range of external stimuli. Like neutrophils, resident macrophages can ingest and kill bacteria, but perhaps their major role in acute inflammation is to initiate and orchestrate the inflammatory response by the secretion of important cytokines (see table 1.4) and chemokines. For example, they can secrete large quantities of the neutrophil chemokine IL-8 and other chemokines that specifically attract monocytes to the inflamed site. These monocytes rapidly mature into inflammatory macrophages, which have huge phagocytic and bacterial killing capacity and which also have important scavenging function for damaged microorganisms and proteins and for aged and damaged host cells in the ‘clearing up’ processes during the resolution of the inflammatory response. Finally, resident and inflammatory macrophages can secrete a range of cytokines that are responsible for tissue repair processes, but clearly in effective control of these processes may underlie the excessive fibroproliferative response that characterizes chronic inflammatory diseases such as pyelonephritis and fibrosing alveolitis (see the information box).  

From the book of:

DAVIDSON’S

Principles and Practice of Medicine

Eighteenth Edition

   

Some examples of diseases featuring an inappropriate or excessive inflammatory response

Acute inflammatory tissue injury (neutrophil dominant)

·          Acute respiratory distress syndrome (ARDS) ·          Acute gout ·          Myocardial infarction/reperfusion injury ·          Acute glomerulonephritis

Chronic Inflammation (lymphocyte/macrophage dominant ± fibrosis)

·          Fibrosing alveolitis ·          Chronic bronchitis and emphysema ·          Chronic pyelonephritis ·          Atherogenesis ·          Rheumatoid arthritis ·          Psoriasis ·          Multiple sclerosis

Chronic allergic inflammation (lymphocytes and esinophil dominant)

·          Bronchial asthma ·          Eczema

The Cellular Players

The neutrophil granulocyte

Neutrophils are short-lived, bone marrow-derived (half-life 6 hours), circulating white blood cells with a diameter of about 5.5 µM. on ultrastructure (see fig: 1.20) they contain a large number of cytoplasmic granules, which in turn contain a large number of powerful agents (see table 1.2), many of which when secreted can aid the cell’s rapid transit through tissues, and prompt phagocytosis and destruction of bacteria. Neutrophils are the archetypal acute inflammatory cells they are highly responsive to chemotactic mediators, e.g. IL-8 and C5a, and are the first cells to emigrate to the inflamed site (see below). The importance of the neutrophils in host defense is emphasized by the greatly increased susceptibility to infection found in patients with neutropenia or inherited disorders of neutrophil function. A number of diseases have been linked with rare inherited abnormalities in neutrophil granules. Most of these are characterized by repeated bacterial infections. Chronic granulomatous disease due to a defect in NADPH oxidase is perhaps the best-recognized example.

 

Table 1.2 Constituents of human neutrophil granules
	Azurophil granules	Specific granules
Microbicidal enzymes	Lysozyme Myeloperoxidase	Lysozyme
Neutral proteinases	Elastase Collagenases Cathepsin G	Collagenase
Acid hydrolases	Phosphatases Lipases Sulphatases Histonase Cathepsin D B glycerophosphatase Esterase Neuraminidase 5’ nucleotidase	Phosphatases
Others	Bactericidal/ Permeability-inducing protein Defensins Cationic proteins Glycosaminoglycans Chondroitin sulphate Heparin sulphate	Lactoferrin Vitamin B12 binding protein C3bi receptor Cytochrome B Flavoproteins