{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Khan SQ"],"funding":["NIDDK NIH HHS","NHLBI NIH HHS"],"pagination":["45"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4291902"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["1"],"pubmed_abstract":["Kidney allograft rejection is associated with infiltration of inflammatory CD11b+ leukocytes. A CD11b agonist leukadherin-1 (LA1) increases leukocyte adhesion, preventing their transmigration and tissue recruitment in vivo. Here, we test the extent to which LA1-mediated activation of CD11b/CD18 enhances kidney allograft survival in a mouse model of fully MHC-mismatched orthotopic kidney transplantation, where C57BL/6J (H-2(b)) recipients received kidney allografts from Balb/c mice (H-2(d)). Isograft control recipients received a kidney from a littermate. Control isograft and allograft recipients were treated daily with cyclosporine (CsA) for 2 weeks, while the test group received CsA therapy and daily LA1 injections during week 1 and alternate days during weeks 2-8. LA1 treatment reduced interstitial leukocyte infiltration in the allograft, reduced neointimal hyperplasia and glomerular damage, and prolonged graft survival from 48.5% (CsA only) to 100% (CsA and LA1) on day 60. Serum creatinine levels showed significantly improved kidney function in LA1-treated mice compared to CsA-treated allograft controls [0.52 ± 0.18 mg/dL vs 0.24 ± 0.07 mg/dL (n = 5), respectively]. Furthermore, combination therapy reduced macrophage infiltration and increased the frequency of FoxP3 + Tregs in the allograft. These findings indicate a crucial role for CD11b/CD18 in the control of leukocyte migration to the transplanted kidney and identify integrin agonist LA1 as a novel potential therapeutic agent for kidney transplantation."],"journal":["Frontiers in medicine"],"pubmed_title":["A Small Molecule β2 Integrin Agonist Improves Chronic Kidney Allograft Survival by Reducing Leukocyte Recruitment and Accompanying Vasculopathy."],"pmcid":["PMC4291902"],"funding_grant_id":["R01 HL109582","P30 DK079337","R01 DK084195"],"pubmed_authors":["Khan SQ","Cimbaluk DJ","Guo L","Agarwal A","Gupta V","Elshabrawy H","Faridi MH","Jolly M","George JF"],"additional_accession":[]},"is_claimable":false,"name":"A Small Molecule β2 Integrin Agonist Improves Chronic Kidney Allograft Survival by Reducing Leukocyte Recruitment and Accompanying Vasculopathy.","description":"Kidney allograft rejection is associated with infiltration of inflammatory CD11b+ leukocytes. A CD11b agonist leukadherin-1 (LA1) increases leukocyte adhesion, preventing their transmigration and tissue recruitment in vivo. Here, we test the extent to which LA1-mediated activation of CD11b/CD18 enhances kidney allograft survival in a mouse model of fully MHC-mismatched orthotopic kidney transplantation, where C57BL/6J (H-2(b)) recipients received kidney allografts from Balb/c mice (H-2(d)). Isograft control recipients received a kidney from a littermate. Control isograft and allograft recipients were treated daily with cyclosporine (CsA) for 2 weeks, while the test group received CsA therapy and daily LA1 injections during week 1 and alternate days during weeks 2-8. LA1 treatment reduced interstitial leukocyte infiltration in the allograft, reduced neointimal hyperplasia and glomerular damage, and prolonged graft survival from 48.5% (CsA only) to 100% (CsA and LA1) on day 60. Serum creatinine levels showed significantly improved kidney function in LA1-treated mice compared to CsA-treated allograft controls [0.52 ± 0.18 mg/dL vs 0.24 ± 0.07 mg/dL (n = 5), respectively]. Furthermore, combination therapy reduced macrophage infiltration and increased the frequency of FoxP3 + Tregs in the allograft. These findings indicate a crucial role for CD11b/CD18 in the control of leukocyte migration to the transplanted kidney and identify integrin agonist LA1 as a novel potential therapeutic agent for kidney transplantation.","dates":{"release":"2014-01-01T00:00:00Z","publication":"2014","modification":"2025-04-21T15:59:06.177Z","creation":"2019-03-27T01:43:20Z"},"accession":"S-EPMC4291902","cross_references":{"pubmed":["25593918"],"doi":["10.3389/fmed.2014.00045"]}}