Mesangial cell-derived transforming growth factor-beta 1 reduces macrophage adhesiveness with consequent deactivation

Abstract

Adhesion of macrophages is a crucial event that determines the number and function of macrophages at inflammatory sites. The aim of this study was to elucidate the role of mesangial cells in the regulation of macrophage adhesiveness. J774.2 macrophages were suspended in serial dilutions of mesangial cell conditioned medium (MC medium) and seeded on plastic tissue culture plates. MC medium did not affect the initial adhesion of macrophages but induced subsequent detachment in a concentration-dependent manner. A similar effect was observed when macrophages were plated on plastic coated with laminin, collagen type IV or Matrigel. The reduced adhesiveness was reversible, and cell viability was unaffected by MC medium, indicating that the effect is not due to cytotoxicity. Conditioned media from fibroblastic, epithelial and endothelial cell lines did not induce macrophage detachment. To identify the active component in MC medium, we examined the involvement of transforming growth factor-beta 1 (TGF-beta 1) in the process. Mesangial cells constitutively expressed TGF-beta 1 mRNA, and MC medium contained the active form of TGF-beta 1. Exogenously added TGF-beta 1 induced macrophage detachment in a dose-dependent manner, and an anti-TGF-beta 1 neutralizing antibody partially abolished the activity of MC medium, indicating the involvement of TGF-beta 1 as an active component. Compared to adherent cells, detached macrophages showed reduced mitogenic activity and blunted induction of IL-1 beta and IL-6 in response to lipopolysaccharide. These data demonstrate that TGF-beta 1 is a mesangial cell-derived factor that impairs adhesiveness of macrophages and confers blunted responses to a specific stimulus. These findings suggest one potential mechanism for macrophage clearance from inflamed glomeruli.