Regulation of leukocyte adhesion to heart by the tripeptides feG and feG(NH2)

The role of the D-isomeric form of the salivary gland tripeptide FEG (feG) and its carboxyl-amidated derivative, feG(NH2), in regulating leukocyte adh erence to nonfixed atrial slices from Sprague-Dawley rats was examined unde r static conditions. Optimal binding of the leukocytes was seen if the leuk ocytes were treated with platelet activating factor (PAF; 10(-9)M). The inc reased adherence of PAF-treated peripheral blood leukocytes was totally inh ibited by both feG and feG(NH2) (10(-9)M), as well as by antibodies against CD18 and CD49d. In contrast, the binding of peritoneal leukocytes was bloc ked only by CD49d antibody. Circulating leukocytes obtained from lipopolysa ccharide (LPS) treated (2 mg/kg ip) rats did not bind to atrial slices obta ined from normal hearts, but readily bound to atrial slices obtained from L PS-treated rats. This leukocyte binding was inhibited by in vivo feG treatm ent (100 mug/kg ip, 24 h before harvest) or by treating the isolated cells with feG (10(-9)M). The amidated peptide feG(NH2) reduced neutrophil accumu lation in the atrium elicited by ip injection of LPS, whereas feG was ineff ective. The reduction in neutrophil infiltration into the myocardium by feG (NH2) and the prevention of leukocyte interaction with myocytes seen with b oth feG and feG(NH2) probably results in hindered leukocyte migration in th e inflamed heart, resulting in less tissue damage. The inhibition by these tripeptides on neutrophil adhesion to myocytes suggests that salivary gland s hormones regulate the severity of cardiac inflammation.