Role of adenosine in platelet-mediated reduction in pulmonary vascular permeability.
Previous studies have shown that platelets decrease 125I-labeled albumin permeability across confluent bovine pulmonary artery endothelial cell monolayers. In the current study, we addressed the role of platelets and platelet-derived adenosine (ADO) in vascular barrier function with cultured endothelial cells and isolated perfused lungs. Both 7 x 10(7) platelets/ml and conditioned media prepared from the same concentration of platelets reduced albumin permeability of endothelial monolayers by 37%. This activity was abolished by pretreatment of the platelets with adenosine deaminase (ADA). ADO (10(-7) M) added directly to the monolayer reduced permeability by 19%. Dipyridamole (10(-6) M), an inhibitor of facilitated ADO uptake, was used to evaluate the contribution of endothelial uptake of ADO in the platelet effect. Dipyridamole pretreatment of the endothelial monolayer did not alter the ability of platelets to decrease albumin permeability. Addition of either an A1- or A2-receptor-specific analogue of ADO to endothelial monolayers revealed that only the A1-analogue possessed permeability-decreasing activity. An isolated perfused guinea pig lung model was used to evaluate the effect of platelets on transvascular water flux as measured by the capillary filtration coefficient (Kf,c). Platelets (4.5 x 10(7) platelets/ml) added to the perfusate reduced Kf,c by 29%. Pretreatment of platelets with ADA abolished this response. The addition of ADO (10(-7) M) reduced Kf,c by 11%. Pulmonary vascular resistance was not changed by any intervention. Our results indicate that ADO is a component in platelet-mediated decreases both in albumin permeability across endothelial monolayers and of the capillary filtration coefficient in isolated perfused lungs.
Paty
P S
PS
Department of Physiology and Cell Biology, Albany Medical College, New York 12208.
Sherman
P F
PF
Shepard
J M
JM
Malik
A B
AB
Kaplan
J E
JE
D000241:Adenosine / Q000494:pharmacology / Q000502:physiology*; D000243:Adenosine Deaminase / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002199:Capillary Permeability / Q000187:drug effects*; D002417:Cattle; D004176:Dipyridamole / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D011651:Pulmonary Artery; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*
D004176:Dipyridamole; D000243:Adenosine Deaminase; D000241:Adenosine