© 1999 American Heart Association, Inc.
Original Contributions |
Emigrated Neutrophils Regulate Ventricular Contractility via 
4 Integrin
From the Department of Physiology and Biophysics and Immunology Research Group, University of Calgary, Calgary, Alberta, Canada.
Correspondence to P. Kubes, Immunology Research Group, Health Sciences Centre, University of Calgary, 3330 Hospital Dr NW, Calgary, Alberta T2N 4N1, Canada. E-mail pkubes{at}ucalgary.ca
Abstract—We have previously
shown that CD18 and 
4 integrin were important in the
adherence of emigrated neutrophils to cardiac myocytes. Whether either
of these molecules is important in myocyte dysfunction is unclear. In
this study, we measured contractility as an index of
myocyte function. Control contractility was compared
with shortening response in myocytes exposed to neutrophils in the
presence and absence of anti-CD18 or anti-4 antibodies.
Control unloaded cell shortening, expressed as a percentage of resting
cell length, measured 10.06±1.16% (n=10) at 5 minutes. Circulating
neutrophils caused a 35% reduction in cell shortening, an event
prevented by anti-CD18, but not by anti-4 antibody. When
emigrated neutrophils were added to the myocytes, a profound reduction
(50%) in unloaded cell shortening was noted. A significant increase in
CD18 and 4 integrin was found on emigrated neutrophils.
Addition of anti-CD18 antibody did not protect the myocyte from the
emigrated neutrophils, whereas the addition of an anti-4
antibody significantly reduced neutrophil-induced cell shortening,
despite some neutrophils still adhering to the myocytes. Furthermore,
emigrated neutrophils were able to cause myocytes to go into
contracture within 5 minutes in the presence of neutrophils with or
without anti-CD18 antibody. In addition to the impairment in unloaded
cell shortening, at later times (10 minutes), neutrophils also caused a
40% reduction in the rate of contraction and relaxation. The addition
of either anti-CD18 or anti-4 antibody protected the
myocytes from these changes. The data suggest that immunosuppression of
CD18 on emigrated neutrophils was only partially effective in reducing
myocyte dysfunction. In contrast, immunosuppression of the
4 integrin alone was sufficient to dramatically reduce
all parameters of cell dysfunction measured in this
study.
Key Words: myocyte • emigrated neutrophil • ischemia/reperfusion • contractility • 4 integrin
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