The biologic role of B2 integrins in the host response to expanded polytetrafluoroethylene.
We hypothesized that the adherence of leukocytes to a vascular graft surface is mediated by B2 integrins. We studied integrin expression and monoclonal antibody inhibition of peripheral blood leukocyte (PBL) binding in vitro and CD11b expression in vivo. Human PBL were grown on ePTFE in culture and labeled with monoclonal antibodies to CD11a, -b, -c, and/or CD18. Percentage of monoclonal antibody binding and inhibition of leukocyte adherence was studied for up to 30 min using flow cytometry. ePTFE segments were implanted subcutaneously in SH-1 mice and PBL harvested 4 days later. PBL binding of monoclonal antibodies against CD11b was measured using flow cytometry. CD18 was constitutively expressed and CD11a decreased over time. CD11b increased from 41 to 62% and CD11c increased transiently (P < 0.003, P < 0.005). Inhibiton of PBL adherence was greatest by CD11b (34%) and CD11b + CD18 (57%) (P < 0.005, P < 0.0025). Implanted ePTFE caused a fourfold increase in PBL monoclonal antibody binding of CD11b (P < 0.001) compared to sham, Staphylococcus aureus alone, and combination of ePTFE and S. aureus. In conclusion, leukocyte integrins play a central role in the interaction between PBLs and ePTFE as measured by binding of monoclonal antibodies and inhibition of PBL adherence. This is also true in vivo since PBL increase CD11b expression four times when ePTFE is compared to sham. These observations indicate a potential role in vivo for B2 integrins in vascular prosthetic infections.
Benton
L D
LD
Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903, USA.
Purohit
U
U
Khan
M
M
Greco
R S
RS
D000818:Animals; D000911:Antibodies, Monoclonal; D001667:Binding, Competitive / Q000276:immunology; D018821:CD18 Antigens / Q000032:analysis / Q000502:physiology*; D002448:Cell Adhesion / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006789:Host vs Graft Reaction / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D016167:Integrin alphaXbeta2 / Q000032:analysis; D007962:Leukocytes / Q000737:chemistry; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis; D016177:Macrophage-1 Antigen / Q000032:analysis / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D011138:Polytetrafluoroethylene / Q000494:pharmacology*; D051381:Rats; D016028:Receptors, Leukocyte-Adhesion / Q000187:drug effects
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D016167:Integrin alphaXbeta2; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D016028:Receptors, Leukocyte-Adhesion; D011138:Polytetrafluoroethylene