[Interaction of adenosine with leukocytes and thrombocytes].
Platelets and polymorphonuclear granulocytes (PMN) contribute to post-ischemic myocardial reperfusion damage. However, to elicit any deleterious actions, they first need to become adherent to the vascular endothelium. Numerous studies have documented an A2-receptor mediated platelet-stabilizing action of adenosine and an A2-dependent antiinflammatory effect on PMN themselves. Intriguingly, an A1-receptor mediated chemotactic action of adenosine on isolated PMN has also been reported. A1-receptors are more sensitive towards adenosine than A2-receptors, and interactions between platelets and leukocytes could alter the net-adhesive potential. Furthermore, the endothelial cells also express adenosine A1- and A2-receptors. In the situation of ischemia and reperfusion both, the intracoronary concentration of adenosine and the shear forces, vary with time. We have, therefore, investigated the influence of adenosine on intracoronary adhesion of PMN and platelets, applied to isolated heart preparations (guinea pig), both separately and in combination, and determined the resultant effect on postischemic myocardial pump function. At submicromolar adenosine concentrations, as found after brief ischemia (15 min stopped-flow or 30 min low-flow), adenosine enhanced intracoronary PMN retention by preferentially stimulating endothelial A1-receptors. The effect required the intermediate formation of platelet activating factor (PAF) and occurred via CD11/CD18 adhesion molecules on the PMN. Higher, i.e., micromolar levels of adenosine, in contrast, inhibited PMN adhesion via an A2-receptor dependent mechanism. Thrombin-induced platelet adhesion was inhibited by adenosine at high shear rates by both A1- and A2-receptor dependent mechanisms. However, adenosine was not protective at low shear rates, or at high flow in the presence of PMN. Pertinently, adhesion of either PMN or platelets, alone or in combination, regularly caused deterioration of post-ischemic myocardial function. Thus, depending on its concentration and on the phase of ischemia/reperfusion, adenosine may elicit cardioprotective or detrimental effects in the reperfused myocardium, which makes general prognosis of its role in such situations difficult. However, in the course of every reperfusion, the adenosine levels will inevitably fall into the proadhesive range. Thus, prophylactic inhibition of A1-receptor effects may be beneficial.
Becker
B F
BF
Physiologisches Institut der Universität München.
Zahler
S
S
Seligmann
C
C
Kupatt
C
C
Habazettl
H
H
D000241:Adenosine / Q000502:physiology*; D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D004730:Endothelium, Vascular / Q000503:physiopathology; D006168:Guinea Pigs; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009504:Neutrophils / Q000502:physiology*; D010972:Platelet Activating Factor / Q000502:physiology; D010973:Platelet Adhesiveness / Q000502:physiology; D018047:Receptors, Purinergic P1 / Q000502:physiology
D010972:Platelet Activating Factor; D018047:Receptors, Purinergic P1; D000241:Adenosine
Interaktion von Adenosin mit Leukozyten und Thrombozyten.