Differential effects of monoclonal antibody blockade of adhesion molecules on in vivo susceptibility to soft tissue infection.
Leukocyte adherence to endothelial cells has been implicated in the pathogenesis of microvascular injury as well as in host defense against various infectious microorganisms. Administration of monoclonal antibodies directed against the beta chain of the leukocyte integrins inhibits leukocyte-endothelial-cell adherence and has been reported to modulate ischemia-reperfusion and inflammatory injury. However, such inhibition of adhesion molecule function adversely affects resistance to infection. The following studies were carried out to determine whether monoclonal antibodies to other adhesion molecules, including L-selectin (CD62L), and CD11a (the alpha chain of LFA-1), also increase susceptibility to infection. New Zealand White rabbits were shaved and given subcutaneous injections on their dorsa with 10(9) CFU of Staphylococcus aureus ATCC 25923 at two sites and with 10(8) CFU at two sites. A second set of rabbits were given subcutaneous injections with 10(8) CFU of P. aeruginosa ATCC 27853 at two sites and with 10(7) CFUs at two sites. The animals were monitored for 1 week. There were three blinded experimental groups: controls given saline and two groups given blocking monoclonal antibodies to either L-selectin (Dreg-200) or CD11a (R7.1). In contrast to monoclonal antibodies to CD18, none of the monoclonal antibodies significantly increased the risk of abscess formation by S. aureus, although inhibition of CD11a increased the rate of abscess formation by P. aeruginosa.
Garcia
N
N
Department of Surgery, University of Texas Southwestern Medical Center at Dallas 75235-9031, USA.
Mileski
W J
WJ
Lipsky
P
P
D000038:Abscess / Q000209:etiology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D018821:CD18 Antigens / Q000502:physiology; D004198:Disease Susceptibility; D019041:L-Selectin / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D011817:Rabbits; D012481:Salmonella Infections, Animal / Q000209:etiology*
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D019041:L-Selectin