Evolution and exceptions in inflammatory leukocyte infiltrates
THE CONTEXT
Early neutrophil predominance commonly gives way to longer-lasting macrophage infiltration, but the inflammatory stimulus can alter this pattern.
Why the predominant cell changes
•
Neutrophils predominate early because they are more numerous in blood than other leukocytes, respond more rapidly to chemokines, and may attach more firmly to rapidly induced endothelial adhesion molecules such as P- and E-selectins.
•
After entering tissues, neutrophils are short lived: they undergo apoptosis and disappear within a few days.
•
Monocytes develop into tissue macrophages, which survive longer and may proliferate. Macrophages therefore become dominant in prolonged inflammatory reactions.
•
Following myocardial ischemic necrosis, early infiltrates contain neutrophils and congested vessels, whereas later mononuclear infiltrates consist mostly of macrophages.
•
The kinetics and composition of the infiltrate vary with the severity and cause of the reaction.
Exceptions determined by the stimulus
•
Pseudomonas infections can show neutrophil predominance for several days because neutrophils are continuously recruited.
•
Lymphocytes may be the first cells to arrive in viral infections.
•
Some hypersensitivity reactions are dominated by activated lymphocytes, macrophages, and plasma cells.
•
Eosinophils may predominate in allergic reactions and infections with certain parasites.
Therapeutic relevance
•
Molecular understanding of leukocyte recruitment and migration has provided therapeutic targets for controlling harmful inflammation.
•
TNF is a major cytokine involved in leukocyte recruitment. Agents that block TNF are useful in chronic inflammatory diseases such as rheumatoid arthritis.