Regulation of lipoxins (LX) and leukotriene B4 (LTB4) production in rat mesangial cells (MC).

In the present studies, an inverse relationship was observed between LTB4 and LXA4 formation when the concentration of LTA4 was increased from 50 microM to 250 microM. LTB4 was the major product at low concentration of LTA4 where as LXA4 was the major product at high concentration. This suggests that LTA4 hydrolase activity is present in MC and activated by low concentrations of LTA4. At high concentrations of LTA4, 15- or 12-lipoxygenase (LO) in MC may participat in LXs formation. Radioimmunoassays on HETEs MC activated with A23187 (3uM) were in the rank order of 15-HETE greater than 12-HETE greater than 5-HETE. Incubations of MC with 15-HPETE failed to produce any LX-like material. These results suggest that 1) 5-LO activity is not expressed in MC under these conditions, but LTA4 hydrolase activity is present in MC, 2) there are major activities of 12-LO and 15-LO in MC that are responsible for the generation of LXA4, LXB4 and HETES, 3) the production of LX and 12- or 15-LO products of AA may counterregulate the production of LTB4 and may modulate the response of the MC to inflammatory stimuli.