Effects of Mixed Leukocyte Reaction, Hydrocortisone, or Cyclosporine A on Expression of Adhesion Molecules by Endothelial and Mesangial cells / 대한내과학회지

OBJECTIVES: ICAM-1, VCAM-1, and betal integrins mediate cell-cell or cell-matrix interactions. We investigated effects of mixed leukocyte reaction (MLR), cyclosporine A (CsA), or hydrocortisone (HC) on their expression by endothelial (EnC) and mesangial cells (MC). METHODS: MLR was performed with or without CsA or HC for 5 days. After adding 25N MLR supernatant, cytokines or CsA to MC or EnC, the expression of VCAM-1, ICAM-1, and alpha3beta1 and a501 integrins was examined by using cell surface enzyme immunoassays or flow cytometry. RESULTS: MLR supernatant induced a marked increase in the expression of ICAM-1 and VCAM-1 on MC or EnC(p<0.001). HC treatment during MLR effectively inhibited MLR-induced upregulation of VCAM-1 and ICAM-1 on both cells (p<0.005). HC had, however, no inhibitory effect on VCAM-1 expression when added with MLR supernatant to cells. CsA treatment during MLR caused a modest decrease in MLR-induced expression of VCAM-1 on EnC, but had no effect on that of ICAM-1. INFgamma or TGFbeta1 stimulated expression of VCAM-1, and INFgamma, IL-1beta, or TNF alpha expression of ICAM-1 on MC after 24 hr. INFgamma, or TGFbeta1 enhanced expression of alpha3beta1 or alpha5beta1 integrins on MC after 5 days. CsA caused a modest decrease in basal expression of VCAM-1, and also decreased the basal, or INFgamma, or TGFbeta1-induced expression of alpha3beta1 and alpha5beta1 integrins on MC. CONCLUSION: Alloreactive lymphocytes and monocytes upregulate expression of VCAM-1 and ICAM-1 on EnC and MC maybe by secretion of cytokines such as INFgamma, and facilitate leukocytes attachment and following renal or vascular injury. HC effectively prevent the upregulation of VCAM-1 and ICAM-1 by inhibiting the release of cytokines during MLR. CsA did not cause an increase in the expression of VCAM-1 and beta1 integrin.

Effects of mixed leukocyte reaction, hydrocortisone and cyclosporine on expression of leukocyte adhesion molecules by endothelial and mesangial cells

We investigated the effects of mixed leukocyte reaction (MLR), hydrocortisone (HC) and cyclosporine A (CsA) on the expression of leukocyte adhesion molecules on the mesangial (MC) and endothelial cells (EnC). Cell surface enzyme immunoassay showed that INFnu, IL-1beta, or TNF alpha stimulated expression of ICAM-1, or VCAM-1 on MC after 24 hours. Flow cytometric analysis demonstrated that MLR supernatant induced a marked increase in mean fluorescence of or % of cells highly expressing intercellular adhesion molecule(ICAM)-1 or vascular cell adhesion molecule (VCAM)-1 on both cells after 24 hours (p<0.001). HC treatment(300 ng/ml) during MLR effectively inhibited MLR-induced upregulation of ICAM-1 and VCAM-1 on both cells (p<0.005). When MLR supernatant with HC was added to adhesion molecule assay, there was no inhibitory effect of HC on VCAM-1. CsA treatment (500 ng/ml) during MLR caused a modest decrease in upregulation of VCAM-1 on EnC (p<0.05), but had no effects on ICAM-1 on both cells. CsA directly decreased expression of VCAM-1 on MC. In conclusion, alloreactive lymphocytes and monocytes upregulate the expression of VCAM-1 and ICAM-1 on target cells probably by the mediation of cytokines. HC effectively prevents MLR-induced upregulation of VCAM-1 and ICAM-1. CsA does not increase the expression of VCAM-1 and ICAM-1.

Effects of mixed leukocyte reaction, hydrocortisone and cyclosporine on expression of leukocyte adhesion molecules by endothelial and mesangial cells

We investigated the effects of mixed leukocyte reaction (MLR), hydrocortisone (HC) and cyclosporine A (CsA) on the expression of leukocyte adhesion molecules on the mesangial (MC) and endothelial cells (EnC). Cell surface enzyme immunoassay showed that INFnu, IL-1beta, or TNF alpha stimulated expression of ICAM-1, or VCAM-1 on MC after 24 hours. Flow cytometric analysis demonstrated that MLR supernatant induced a marked increase in mean fluorescence of or % of cells highly expressing intercellular adhesion molecule(ICAM)-1 or vascular cell adhesion molecule (VCAM)-1 on both cells after 24 hours (p<0.001). HC treatment(300 ng/ml) during MLR effectively inhibited MLR-induced upregulation of ICAM-1 and VCAM-1 on both cells (p<0.005). When MLR supernatant with HC was added to adhesion molecule assay, there was no inhibitory effect of HC on VCAM-1. CsA treatment (500 ng/ml) during MLR caused a modest decrease in upregulation of VCAM-1 on EnC (p<0.05), but had no effects on ICAM-1 on both cells. CsA directly decreased expression of VCAM-1 on MC. In conclusion, alloreactive lymphocytes and monocytes upregulate the expression of VCAM-1 and ICAM-1 on target cells probably by the mediation of cytokines. HC effectively prevents MLR-induced upregulation of VCAM-1 and ICAM-1. CsA does not increase the expression of VCAM-1 and ICAM-1.