Mechanisms of leukocyte recruitment to atherosclerotic lesions: future prospects.
OBJECTIVE
Leukocyte invasion in the arterial wall is critical in the development of atherosclerotic lesions. This review describes recent advances in the understanding of leukocyte recruitment in atherogenesis and in the development of vulnerable plaque. It also discusses limitations in the current knowledge of this process and how these limitations may be addressed.


RESULTS
The adhesive function of platelets has recently been highlighted as an important recruitment mechanism in atherosclerosis. For example, targeted deficiency of P-selectin in platelets reduces atherosclerosis in mice. Platelets also increase monocyte recruitment in atherosclerosis by secreting chemokines such as platelet factor 4 (CXCL4) or RANTES (CCL5), which trigger monocyte arrest in atherosclerotic arteries. A causal role for RANTES in atherosclerosis was shown by a protective effect of the blockage of RANTES receptors in apolipoprotein E-deficient mice. A similar effect was also demonstrated for the fractalkine receptor CX3CR1. Moreover, the classic chemoattractant LTB4 plays important roles in atherosclerosis, inasmuch as the absence of the principal LTB4 receptor (BLT1) reduces early atherosclerosis in mice. Novel data have also shown that many types of cells in lesions express 5-lipoxygenase, which indicates a rich source of leukotrienes in plaque.


CONCLUSIONS
Recent data provide evidence for the involvement of several adhesive and signalling mechanisms in leukocyte recruitment in atherosclerosis. However, the specific mechanisms that are responsible for the accumulation of proatherogenic leukocytes in lesions are unclear. Detailed study of certain subclasses of leukocytes in the recruitment process will be important in future studies in this field.
Eriksson
Einar E
EE
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. einar.eriksson@fyfa.ki.se
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D001161:Arteriosclerosis / Q000473:pathology / Q000628:therapy*; D000073883:CX3C Chemokine Receptor 1; D002448:Cell Adhesion; D018946:Chemokine CCL5 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D019742:Chemokines, CC / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D010973:Platelet Adhesiveness; D010978:Platelet Factor 4 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D018102:Receptors, Leukotriene B4 / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D015398:Signal Transduction
C483024:CCL5 protein, human; D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D018946:Chemokine CCL5; D018925:Chemokines; D019742:Chemokines, CC; C513240:LTB4R protein, human; D008565:Membrane Proteins; D019707:Receptors, Chemokine; D018102:Receptors, Leukotriene B4; D018048:Receptors, Purinergic P2; D010978:Platelet Factor 4; D001094:Arachidonate 5-Lipoxygenase