Leukotrienes stimulate neutrophil adhesion to mesangial cells: modulation with lipoxins.
We have examined polymorphonuclear neutrophil (PMN) adhesion to mesangial cells (MC) in vitro and have assessed the actions of lipoxygenase (LO) products in this process. On exposure to either leukotriene B4 (LTB4), or leukotriene D4 (LTD4), 111In-labeled PMNs adhere to monolayers of cultured MC. These actions were rapid in onset (less than 5 min) and dependent upon leukotriene concentration (10(-9) to 10(-6) M) and the presence of divalent cations. Adhesion was sustained (0-30 min), and neither LTB4 nor LTD4 was metabolized to inactive products during PMN-MC interaction, as determined by their recovery after reverse-phase high-performance liquid chromatography. LTB4 was a PMN-directed stimulus, whereas LTD4 appeared to act on MC. A monoclonal antibody (TS 1/18) against the CD18 component of the PMN CD18/CD11 adhesion complex inhibited the LTB4-induced response, indicating involvement of this PMN glycoprotein in the adhesion process. In contrast, this antibody did not affect LTD4-induced adhesion, suggesting that this response was mediated by other adhesion epitopes. When added alone, neither lipoxin A4 (LXA4) nor lipoxin B4 (LXB4) provoked PMN adhesion to MC. In contrast, LXA4 and LXB4 at equimolar concentrations attenuated the LTD4- but not LTB4-induced response. Together, these results provide further evidence that LO-derived eicosanoids may constitute important early signals that regulate PMN-MC interaction in glomerular inflammation.
Brady
H R
HR
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Persson
U
U
Ballermann
B J
BJ
Brenner
B M
BM
Serhan
C N
CN
D002448:Cell Adhesion / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000494:pharmacology*; D044045:Lipoxins; D009504:Neutrophils / Q000187:drug effects*; D013189:SRS-A / Q000494:pharmacology*
D006893:Hydroxyeicosatetraenoic Acids; D044045:Lipoxins; D013189:SRS-A; C040527:lipoxin A4; D003609:Dactinomycin; D007975:Leukotriene B4; C042651:lipoxin B4; D003513:Cycloheximide; D006861:Hydrogen Peroxide