Increased expression of neutrophil and monocyte adhesion molecules LFA-1 and Mac-1 and their ligand ICAM-1 and VLA-4 throughout the acute phase of myocardial infarction: possible implications for leukocyte aggregation and microvascular plugging.
OBJECTIVE
This study sought to evaluate expression of adhesion molecules on neutrophils and monocytes throughout the acute phase of myocardial infarction.


BACKGROUND
Neutrophil and monocyte counts increase within days from onset of acute myocardial infarction. Because leukocytes are recruited to the involved myocardial region, we postulated that these activated cells would display an increased expression of adhesion molecules necessary for effective endothelial transmigration.


METHODS
We measured the expression of neutrophil and monocyte lymphocyte function associated antigen-1 (LFA-1), Mac-1, very late after activation antigen-4 (VLA-4) and intercellular adhesion molecule-1 (ICAM-1) by flow cytometry throughout the acute phase of acute myocardial infarction in 25 patients and 10 age-matched control subjects.


RESULTS
Expression of Mac-1 on neutrophils increased significantly, whereas no expression of VLA-4 and ICAM-1 was detected. The expression of LFA-1, Mac-1, VLA-4 and ICAM-1 on the monocyte cell membrane in patients with an acute myocardial infarction was increased compared with that in control subjects by 22% (on day 7), 67%, 13% and 44% (all on day 4), respectively (all p < 0.001). Elevated density of monocyte-specific CD14 in the AMI versus the control group was also shown (30%, p < 0.001).


CONCLUSIONS
Increased expression of neutrophil and monocyte adhesion molecules may contribute to their adhesion to endothelium in the ischemic territory. This adhesion could feasibly precipitate vasoconstriction or add a local thrombotic effect due to tissue factor expression secondary to Mac-1 engagement. In addition, the manifestation of increased density of LFA-1 and Mac-1 by activated leukocytes with monocytes also expressing ICAM-1 suggests that leukocytes may form microaggregates that could cause microvascular plugging. This mechanism may facilitate the occurrence of the "no-reflow" phenomenon or slow coronary filling after acute myocardial infarction.
Meisel
S R
SR
Department of Cardiology, Sackler School of Medicine, Tel Aviv University, Israel.
Shapiro
H
H
Radnay
J
J
Neuman
Y
Y
Khaskia
A R
AR
Gruener
N
N
Pauzner
H
H
David
D
D
D000368:Aged; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000097:blood*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000097:blood*; D016177:Macrophage-1 Antigen / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy / Q000276:immunology*; D018375:Neutrophil Activation; D016201:Receptors, Lymphocyte Homing / Q000097:blood*; D016029:Receptors, Very Late Antigen / Q000097:blood*; D015912:Thrombolytic Therapy
D039041:Integrin alpha4beta1; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D016201:Receptors, Lymphocyte Homing; D016029:Receptors, Very Late Antigen; D018799:Intercellular Adhesion Molecule-1