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 ischemia 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 (approximately 5 micrometers) venous cisterns that average 200 micrometers in length and vary from 10 to 70 micrometers in width and show strong constitutive expression of both ICAM-1 and P-selectin; this class of vessels (venous cisterns) appears to be a unique feature in heart. A monoclonal antibody (SG8H6) with specificity for canine neutrophils was developed that allowed much more sensitive immunohistochemical detection of neutrophils in tissue and allowed us to follow tissue infiltration with time. Samples from 1 hour of reperfusion revealed dense margination and substantial emigration of neutrophils associated with the venous cisterns and collecting venules. By 2 hours, there was intense local emigration to the extravascular space between cardiac myocytes. By 3 hours, the infiltrate extended deeper into the infarct, and there was a continuous border zone of neutrophil infiltration that overlapped a region where intact cardiac myocytes strongly expressed ICAM-1 mRNA and extended into the necrotic tissue. At later times, neutrophil migration into infarcted tissue continued to progress. Neutrophil transmigration into reperfused myocardium is more extensive than previously described, and its extravascular distribution 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 participate in reperfusion injury.
Hawkins
H K
HK
Department of Pathology, University of Texas Medical Branch, TX 77555-0747, USA.
Entman
M L
ML
Zhu
J Y
JY
Youker
K A
KA
Berens
K
K
Doré
M
M
Smith
C W
CW
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal; D003331:Coronary Vessels / Q000473:pathology; D004285:Dogs; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000235:genetics; D007958:Leukocyte Count; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000473:pathology*; D009206:Myocardium / Q000737:chemistry / Q000276:immunology / Q000473:pathology*; D009336:Necrosis; D009504:Neutrophils / Q000473:pathology*; D019007:P-Selectin / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis
D000911:Antibodies, Monoclonal; D019007:P-Selectin; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1