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

Gastroenterology. 1993 Jan;104(1):31-7. doi: 10.1016/0016-5085(93)90832-w.


Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine / pharmacology*
  • Animals
  • Cell Adhesion / drug effects
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / physiology
  • Leukocyte Adherence Inhibition Test
  • Leukocytes / physiology*
  • Leukotriene B4 / pharmacology
  • Male
  • Methotrexate / pharmacology*
  • Platelet Activating Factor / pharmacology
  • Purinergic Antagonists
  • Rats
  • Rats, Sprague-Dawley
  • Splanchnic Circulation*
  • Venules / cytology
  • Venules / physiology


  • Platelet Activating Factor
  • Purinergic Antagonists
  • Leukotriene B4
  • Adenosine
  • Methotrexate