title: Chemoattractants provoke monocyte adhesion to human mesangial cells and mesangial cell injury.
abstract: Infiltration of glomerular mesangium by monocytes/macrophages is a prominent pathologic finding in many forms of glomerulonephritis (GN). While the mechanism(s) by which infiltration occurs is incompletely understood, monocyte adhesion to glomerular endothelial cells, provoked by inflammatory mediators, appears to be an important early step. In the present study, we assessed the influence of chemotactic peptides (C5a) and lipids (LTB4 and PAF) on adhesion of human monocytes and mesangial cells, to determine if mesangial cells (glomerular pericytes with smooth muscle properties) represent potential targets for adhesion of chemoattractant-activated monocytes following their diapedesis from the intravascular space. C5a and LTB4 provoked rapid (onset less than 1 min) monocyte-mesangial cell adhesion at nanomolar concentrations via actions with monocytes, while PAF was less potent in this regard. Monoclonal antibodies (mAb) were used to define the monocyte and mesangial cell adhesion molecules involved in these interactions. C5a- and LTB4-induced monocyte adhesion was inhibited (approximately 54%) by mAb against the common beta CD18 subunit of CD11/CD18 leukocyte integrins, while mAb against monocyte L-selectin was without effect. MAb against unique CD11 subunits were used to determine the relative contributions of different CD11/CD18 integrins. In this regard, adhesion was inhibited by mAb against CD11b (approximately 41%), and CD11c (approximately 23%), but not CD11a. MAb against mesangial cell ICAM-1 afforded approximately 27% reduction in adhesion, while mAb against VCAM-1, E-selectin, and P-selectin were without effect. GM-CSF, a cytokine generated by monocytes and mesangial cells, also provoked CD11/CD18-dependent adhesion, and primed monocytes to the actions of chemoattractants.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, Brigham & Women's Hospital, Boston, Massachusetts.
authors.forename: H R
authors.initials: HR
authors.lastname: Brady
authors.forename: M D
authors.initials: MD
authors.lastname: Denton
authors.forename: W
authors.initials: W
authors.lastname: Jimenez
authors.forename: S
authors.initials: S
authors.lastname: Takata
authors.forename: D
authors.initials: D
authors.lastname: Palliser
authors.forename: B M
authors.initials: BM
authors.lastname: Brenner
mesh_terms: D000911:Antibodies, Monoclonal; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D015936:Complement C5a / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000166:cytology* / Q000187:drug effects / Q000293:injuries; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000502:physiology; D007975:Leukotriene B4 / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C060636:1-O-alkyl-2-propionyl-sn-glycero-3-phosphocholine; D000911:Antibodies, Monoclonal; D016207:Cytokines; D016023:Integrins; D010972:Platelet Activating Factor; D007975:Leukotriene B4; D015936:Complement C5a; D016178:Granulocyte-Macrophage Colony-Stimulating Factor