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Fanning the flames: inflammation in cardiovascular diseases.

Leucocytes have occupied centre stage as protagonists in host defences and inflammatory diseases since the era of the 19th century pioneers including Virchow, Cohnheim, and Metchnikoff.1 These investigators helped establish the scientific basis of modern medicine through their careful morphologic observation, experimental manipulations, and deductive reasoning. The romance of the white corpuscle achieved popular culture status in the beginning of the 20th century, as reflected by George Bernard Shaw's exhortation to ‘stimulate the phagocytes’ in his 1906 play ‘The Doctor's Dilemma’.2

Application of the tools of biochemistry and cell biology enabled fleshing out the functions of phagocytes in the 20th century. Such studies discovered the ability of leucocytes to produce reactive oxygen species (ROS), lipid mediators, peptides, and cytokines, as well as granular constituents including plentiful proteinases. This potent armamentarium equips leucocytes to fight invaders, or when turned against the host, to produce or promote disease.

The field of leucocyte biology has flourished during the last several decades. We now possess detailed knowledge of the way in which various leucocyte sub-classes enter, tarry within, and exit the vasculature and tissue compartments ( Figure 1 ). We have learned what signals beckon these cells to extravasate and delineated detailed mechanisms by which they do so. Leucocytes not only enter tissues but persist within them in response to specific signals, and may in some cases emigrate, each step subject to regulation by various interesting mechanisms and paths. 



Figure 1 
( A ) This panel shows a simplified ‘life cycle’ of neutrophil responding to an acute inflammatory or injurious stimulus. The role of the neutrophil typically plays out in a matter of hours. The neutrophil can exercise functions intravascularly, in interstitial spaces, in walled-off collections (abscesses), or within the parenchyma of a tissue. After recruitment and activation, neutrophils release many …