Roles of arachidonate metabolites in thrombus formation and leukocyte migration: Analyses at microcirculatory level.

Thromboxane (TX) A2 is involved in platelet aggregation, which initiates thrombus formation. The platelet thrombi in microcirculation, however, are not homogeneous in nature. Two types of platelet thrombi, formed in an arteriole of the hamster cheek pouch, could be differentiated in sensitivity to indomethacin and PGI2. The "stable thrombus" was sensitive to indomethacin, and was not inhibited by PGI2, when applied after the formation, whereas the "ADP-induced thrombus" was sensitive to PGI2, but insensitive to indomethacin. These characteristics were reflected by two types of aggregation of composed platelets. Leukotriene B4 induced adhesion of the leukocytes on the venular wall in very low concentrations, when perfused over the microvasculature of hamster cheek pouch. The leukocyte adhesion on the venular wall was followed by migration into interstitial space. This adhesion was attributed to a change of leukocytes, rather than of the endothelial cell surface, as ascertained by selective microinjection of LTB4 with a glass capillary. LTB4 was also accumulated in the ischemic cardiac tissue after ligation of the rat coronary artery, followed by a peak in the accumulation of leukocytes. Inhibition of the LTB4 generation by a 5-lipoxygenase inhibitor not only suppressed the leukocyte count by 40%, but also the infarct size by 34.4%.