Role of anti-L-selectin antibody in burn and smoke inhalation injury in sheep

Abstract

We hypothesized that the antibody neutralization of L-selectin would decrease the pulmonary abnormalities characteristic of burn and smoke inhalation injury. Three groups of sheep ( n = 18) were prepared and randomized: the LAM-(1–3) group ( n = 6) was injected intravenously with 1 mg/kg of leukocyte adhesion molecule (LAM)-(1-3) (mouse monoclonal antibody against L-selectin) 1 h after the injury, the control group ( n = 6) was not injured or treated, and the nontreatment group ( n = 6) was injured but not treated. All animals were mechanically ventilated during the 48-h experimental period. The ratio of arterial Po 2 to inspired O2 fraction decreased in the LAM-(1–3) and nontreatment groups. Lung lymph flow and pulmonary microvascular permeability were elevated after injury. This elevation was significantly reduced when LAM-(1–3) was administered 1 h after injury. Nitrate/nitrite (NO x ) amounts in plasma and lung lymph increased significantly after the combined injury. These changes were attenuated by posttreatment with LAM-(1–3). These results suggest that the changes in pulmonary transvascular fluid flux result from injury of lung endothelium by polymorphonuclear leukocytes. In conclusion, posttreatment with the antibody for L-selectin improved lung lymph flow and permeability index. L-selectin appears to be principally involved in the increased pulmonary transvascular fluid flux observed with burn/smoke insult. L-selectin may be a useful target in the treatment of acute lung injury after burn and smoke inhalation.

Combined anticoagulants ameliorate acute lung injury in sheep after burn and smoke inhalation

“…Accordingly, in the present study, we also showed that combined anticoagulant therapy significantly reduced the increase in lung tissue MPO activity. We have also shown previously that inhibition of L-selectin resulted in a marked reduction in pulmonary transvascular fluid flux and lung oedema [29]. Antithrombin suppresses leucocyte activation through inhibiting NF-κB [30] and affects neutrophil migration via its heparin-binding site interacting with cell-surface syndecan-4 [5,31], a transmembrane receptor expressed on multiple cell types including neutrophils.…”

The effect of anti-L-selectin (aselizumab) in multiple traumatized patients—Results of a phase II clinical trial*

“…Thus, L-selectin antagonists could interfere with neutrophil adhesion. In experimental studies, blocking of Lselectin reduced the remote lung injury after infrarenal ischemia reperfusion injury (6) without increasing the risk of infection, improved survival in a baboon trauma model (7), and diminished pulmonary microvascular permeability in burn and smoke injury (8). In view of the experimental studies, as well as the role of L-selectin in the development of posttraumatic organ failure (9), blocking L-selectin may also attenuate recruitment of leukocytes in the posttraumatic inflammatory response and, thus, might decrease the rate of MOF in multiple traumatized patients.…”

P-selectin blockade fails to improve acute lung injury in sheep

“…There are several studies reporting that selectins might be involved in cell activation [16]. This may be why we were able to block much of the pulmonary microvascular response with the administration of LAM1-3, the F(ab) # portion of the monoclonal antibody to L-selectin [3,17]. The anti-(P-selectin) antibody may not prevent the activation process involved in deposition of leucocytes in the pulmonary microcirculation (i.e.…”