Am. J. Respir. Crit. Care Med., Vol 152, No. 4, 10 1995, 1331-1336.
Anti-CD18 antibody does not block ileal injury induced by phorbol myristate acetate
MC Overdahl, MW Julian, SE Weisbrode and PM Dorinsky
Department of Medicine, Ohio State University Medical Center, Columbus 43210, USA.
Acute lung injury (ALI) is frequently complicated by systemic microvascular
injury. In previous studies, ALI from acid aspiration resulted in ileal
microvascular injury. This was due to systemic inflammation and was
prevented by MoAb 60.3, an antibody against the CD18 antigen that mediates
leukocyte adherence. The present study was designed to test the hypothesis
that ileal microvascular injury during phorbol myristate acetate
(PMA)-induced systemic inflammation is also blocked by MoAB 60.3. We
assessed the injury by measuring the concentration ratios of lymph protein
to plasma protein (i.e., CL/CP) at steady-state lymph flows in autoperfused
cat ileum preparations. As expected, the CL/CP increased in the ilea of
animals given PMA (15 micrograms/kg; n = 5) compared with the ilea of
control animals (n = 5) (0.202 +/- 0.024 versus 0.106 +/- 0.010; p = 0.006)
and was accompanied by widespread morphologic alterations. Intravenously
administering MoAb 60.3 (2 mg/kg) to animals before the PMA infusion (n =
5) yielded a CL/CP value indistinguishable from that of the PMA group
(0.222 +/- 0.024 versus 0.202 +/- 0.024; p = NS). These results suggest
that CD18- mediated leukocyte adherence is not important in the mechanism
of PMA- induced ileal microvascular injury.
