title: Inhibition of leukocyte adherence and susceptibility to infection.
abstract: Leukocyte (WBC) adherence to endothelial cells (EC) has been implicated in the pathogenesis of microvascular injury. WBC-EC adherence is largely dependent on interaction between the WBC-CD18 complex and the endothelial ligand, intercellular adhesion molecule-1 (ICAM-1). Administration of monoclonal antibodies directed against CD18 and/or ICAM-1 inhibit WBC-EC adherence and have been reported to modulate ischemia-reperfusion and inflammatory injury. We asked the question, does inhibition of WBC-EC adherence by administration of monoclonal antibody directed against either CD18 (R15.7) or against ICAM-1 (R6.5) increase susceptibility to infection. New Zealand white rabbits were shaved and injected subcutaneously on their dorsum with Staphylococcus aureus (ATCC No. 25923) at two sites each with 10(9), 10(8), 10(7), and 10(6) colony-forming units (CFUs). A second set of rabbits were injected subcutaneously with Pseudomonas aeruginosa (ATCC No. 27853) at two sites each of 10(8) and 10(7) CFUs. Animals were monitored for 1 week with daily determination of weight, temperature, WBC counts, hematocrit, and gross evidence of abscess formation. There were three blinded experimental groups; animals given R15.7 (2.0 mg/kg), animals given R6.5 (2.0 mg/kg), and controls given saline (2.0 ml/kg). Administration of the anti-CD18 antibody, R15.7, resulted in significantly increased rates of abscess formation following innoculation with S. aureus and with P. aeruginosa, compared to controls and to the animals given the antibody to ICAM-1, R6.5. The administration of R6.5 did not increase the incidence or severity of abscess formation.
authors.affiliation: Department of Surgery, University of Texas Southwestern Medical Center, Dallas 75235-9031.
authors.forename: W J
authors.initials: WJ
authors.lastname: Mileski
authors.forename: P
authors.initials: P
authors.lastname: Sikes
authors.forename: L
authors.initials: L
authors.lastname: Atiles
authors.forename: E
authors.initials: E
authors.lastname: Lightfoot
authors.forename: P
authors.initials: P
authors.lastname: Lipsky
authors.forename: C
authors.initials: C
authors.lastname: Baxter
mesh_terms: D000038:Abscess / Q000209:etiology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D001831:Body Temperature; D018821:CD18 Antigens; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000276:immunology; D015169:Colony Count, Microbial; D004198:Disease Susceptibility; D018799:Intercellular Adhesion Molecule-1; D007958:Leukocyte Count; D007962:Leukocytes / Q000502:physiology*; D011552:Pseudomonas Infections / Q000209:etiology* / Q000382:microbiology / Q000401:mortality; D011817:Rabbits; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology; D013203:Staphylococcal Infections / Q000209:etiology* / Q000382:microbiology / Q000401:mortality; D016019:Survival Analysis
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D016028:Receptors, Leukocyte-Adhesion; D018799:Intercellular Adhesion Molecule-1