EFFECT OF INHIBITING LEUKOCYTE INTEGRIN (CD18) AND SELECTIN (L-SELECTIN) ON SUSCEPTIBILITY TO INFECTION WITH PSEUDOMONAS-AERUGINOSA

Leukocyte (WBC) adherence to endothelial cells has been implicated in the pathogenesis of microvascular injury. The process of leukocyte adh erence is mediated by both the integrin and selectin families of molec ules, and their interaction with specific endothelial ligands. Antibod ies directed against the leukocyte integrin CD18 and L-selectin have b een developed and functionally inhibit leukocyte adherence in models o f inflammatory injury. We asked the question: Does inhibition of leuko cyte adherence by administration of monoclonal antibody directed again st either CD18, integrins (R15.7, R7.1) or against L-selectin (DREG 20 0) increase susceptibility to infection? New Zealand white rabbits wer e shaved and injected subcutaneously on their dorsum with Pseudomonas aeruginosa (ATCC not-equal 27853) at two sites each of 10(8) and 10(7) colony forming units. Animals were monitored with daily determination of weight, temperature, WBC counts, hematocrit, and killed at 1 week for determination of abscess formation. There were four blinded experi mental groups: (1) Saline (2 mL/kg); (2) DREG 200 (2 mg/kg); (3) R7.1 (2 mg/kg); or (4) R15.7 (2 mg/kg). At the 10(7) and 10(8) injection si tes the R15.7 group had an increased rate and size of abscess formatio n compared with controls. The R7.1 group had an increased rate at the 10(8) injection site. There was no significant difference in the perce ntage of the abscess formation or mean area between the controls and D REG 200-treated groups. We conclude that giving antibody to CD18 incre ased susceptibility to infection while giving antibody to L-selectin d oes not.