Inhibition of leukocyte-endothelial adherence following thermal injury

William Mileski, David Borgstrom, Ellis Lightfoot, Robert Rothlein, Ronald Faanes, Peter Lipsky, Charles Baxter

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Abstract

Progressive microvascular damage in the tissue adjacent to a cutaneous burn injury results in extension of burn size. The role of neutrophils (PMNs) in the pathogenesis of microvascular injury was investigated by inhibition of PMN adherence to the microvascular endothelium using monoclonal antibodies directed to the leukocyte CD18 adhesion complex or its endothelial ligand, intercellular adhesion molecule-1 (ICAM-1, CD54). A model of thermal injury was developed using New Zealand White rabbits. Under general anesthesia two sets of three full-thickness burns separated by two 5 × 30-mm zones were produced by applying brass probes heated to 100°C to the animals' backs for 30 sec. Cutaneous blood flow determinations were obtained for 72 hr. Blood flow measurements were performed using a laser doppler blood flowmeter (PF3, Perimed, Piscataway, NJ). There were five experimental groups; controls given saline alone, n = 12; animals given monoclonal antibody to the PMN CD18 complex, R 15.7 prior to burn injury (pre-R15.7, n = 5); animals given R 15.7 30 min after burn injury (post-R 15.7, n = 6); animals given the anti ICAM-1 antibody, R 6.5 prior to burn (pre-R 6.5, n = 6); and animals given the R 6.5 30 min postburn injury (post-R 6.5, n = 6). BF in the marginal "zone of stasis" between burn contact sites was significantly higher in the antibody-treated animals and administration of the antibodies 30 min after injury was as effective as preburn administration in preserving blood flow. At 72 hr post-burn all antibody-treated animals had blood flow in the areas at risk for progression (i.e., the zone of stasis) at or above baseline levels while the control animals had levels equal to 34.7 ± 12% of baseline (P < 0.05 by analysis of variance and Mann-Whitney U test). These results suggest that PMNs play an important role in the pathogenesis of burn wound progression, and that this progression can be attenuated by modulating PMN-EC adherence.

Original languageEnglish (US)
Pages (from-to)334-339
Number of pages6
JournalJournal of Surgical Research
Volume52
Issue number4
DOIs
StatePublished - 1992
Externally publishedYes

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ASJC Scopus subject areas

  • Surgery

Cite this

Mileski, W., Borgstrom, D., Lightfoot, E., Rothlein, R., Faanes, R., Lipsky, P., & Baxter, C. (1992). Inhibition of leukocyte-endothelial adherence following thermal injury. Journal of Surgical Research, 52(4), 334-339. https://doi.org/10.1016/0022-4804(92)90112-D