Leukocyte adherence in rat mesenteric venules: effects of adenosine and methotrexate.

Abstract

Methotrexate (MTX) reduces neutrophil adhesion to endothelial cell monolayers, possibly via stimulation of adenosine production. However, it remains unclear whether adenosine participates in the anti-inflammatory actions of MTX in postcapillary venules. Leukocyte-endothelial cell adhesive interactions were measured in rat mesenteric venules (25-35 microns diameter) during superfusion with either bicarbonate-buffered saline (BBS) alone, BBS combined with platelet-activating factor (PAF), or BBS combined with leukotriene B4 (LTB4). In some experiments, either MTX or adenosine was added to a superfusate containing either PAF or LTB4. In other experiments, either adenosine deaminase (ADA), an adenosine A1-receptor antagonist, or an A2-receptor antagonist was added to a superfusate containing PAF and either MTX or adenosine. Both MTX and adenosine were effective in preventing the leukocyte-endothelial cell adhesive interactions elicited by PAF, but not by LTB4. These actions of adenosine and MTX against PAF-induced leukocyte adhesion were blunted by ADA and the A2-(but not the A1-) receptor antagonist. These results indicate that both adenosine and methotrexate attenuate PAF-induced leukocyte-endothelial cell adhesion in postcapillary venules via activation of A2-receptors on the leukocyte.