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