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Inhibition of leukocyte-endothelial adherence following thermal injury
W Mileski1, D Borgstrom, E Lightfoot
1Department of Surgery, University of Texas Southwestern Medical School, Dallas 75235-9031.
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 x 30-mm zones were produced by applying brass probes heated to 100 degrees 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Blocking neutrophil adherence with antibodies targeting CD18 or ICAM-1 significantly improved blood flow in burn-injured tissue. This suggests a key role for neutrophils in burn-induced microvascular damage, with therapeutic potential even when administered post-injury.
Area of Science:
- Wound Healing Research
- Immunology
- Microcirculation Studies
Background:
- Cutaneous burn injuries cause progressive microvascular damage, leading to increased burn size.
- Neutrophils (PMNs) are implicated in the pathogenesis of this microvascular injury.
Purpose of the Study:
- To investigate the role of neutrophils in burn-induced microvascular injury.
- To evaluate the efficacy of inhibiting neutrophil adherence using monoclonal antibodies against CD18 or ICAM-1.
Main Methods:
- A thermal injury model was established in New Zealand White rabbits.
- Monoclonal antibodies targeting the CD18 complex or ICAM-1 were administered before or after burn injury.
- Cutaneous blood flow was measured using a laser Doppler flowmeter for 72 hours.
Main Results:
- Antibody treatment significantly increased blood flow in the "zone of stasis" adjacent to burns.
- Administering antibodies 30 minutes post-injury was as effective as pre-injury administration.
- Neutrophil adherence inhibition preserved microvascular blood flow.
Conclusions:
- Neutrophils play a critical role in burn-induced microvascular damage.
- Inhibiting neutrophil adherence via CD18 or ICAM-1 is a promising therapeutic strategy.
- Therapeutic intervention targeting neutrophils can be effective even when initiated after burn injury.