ACUTE INFLAMMATORY REACTION AFTER MYOCARDIAL ISCHEMIC-INJURY AND REPERFUSION - DEVELOPMENT AND USE OF A NEUTROPHIL-SPECIFIC ANTIBODY

Reperfusion of the infarcted canine myocardium after 1 hour of ischemi a is associated with an acute inflammatory infiltrate at the border of the infarct. In this paper, we demonstrate that early margination and emigration of neutrophils originate in thin-walled (similar to 5-mu m ) venous cisterns that average 200 mu m in length and vary from 10 to 70 mu m in width and show strong constitutive expression of both ICAM- 1 and P-selectin; this class of vessels (venous cisterns) appears to b e a unique feature in heart. A monoclonal antibody (SG8H6) with specif icity for canine neutrophils was developed that allowed much more sens itive immunohistochemical detection of neutrophils is tissue and allow ed us to follow tissue infiltration with time. Samples from 1 hour of reperfusion revealed dense margination and substantial emigration of n eutrophils associated with the venous cisterns and collecting venules. By 2 hours, there was intense local emigration to the extravascular s pace between cardiac myocytes. By 3 hours, the infiltrate extended dee per into the infarct, and there was a continuous border zone of neutro phil infiltration that overlapped a region where intact cardiac myocyt es strongly expressed ICAM-1 mRNA and extended into the necrotic tissu e. At later times, neutrophil migration into infarcted tissue continue d to progress. Neutrophil transmigration into reperfused myocardium is more extensive than previously described and its extravascular distri bution during early reperfusion is primarily in the viable border zone of the myocardium where myocyte ICAM-1 mRNA is found. These data are compatible with the hypothesis that extravascular neutrophils may part icipate in reperfusion injury.