Peripheral blood mononuclear cells exhibit hypercatabolic activity in response to thermal injury correlating with diminished MHC I expression.
BACKGROUND
Muscle wasting is one of the major consequences of severe injury or infection. Although the mechanisms underlying this hypercatabolic state are not completely characterized, it was hypothesized that other cells in the body would be similarly affected. In particular, we sought to determine whether lymphoid cell populations experienced increased protein turnover after burn injury in a fashion analogous to that seen in skeletal muscle.


METHODS
BALB/c mice received either a 20% total body surface area burn or a control sham treatment. At days 1, 2, and 7 after treatment, skeletal muscle, peripheral blood, spleen, and lymph nodes were harvested from both groups. Protein synthesis and degradation rates were measured using 14C-phenylalanine incorporation and tyrosine release. Lymphocyte subpopulations (CD4 and CD8 T cells, macrophages, and B cells) and expression of major histocompatibility complex I (MHC I) molecules were assessed by flow cytometry.


RESULTS
The burn model used in this study resulted in increased skeletal muscle protein turnover in the first 2 days after injury. Protein synthetic and degradation rates of peripheral blood mononuclear cells (PBMNCs) in burned mice also demonstrated comparable changes, but persisted through day 7. Splenocytes showed similar hypercatabolic effects, whereas lymph node cells showed no change. Cell viability analysis confirmed that the observed alterations were not caused by cell death. MHC I expression was depressed in tandem with the increased catabolic rate in PBMNCs.


CONCLUSIONS
This study demonstrates that various lymphoid populations undergo protein catabolic changes similar to those characteristically observed in skeletal muscle, and these correlated with diminished MHC I expression. Moreover, PBMNCs exhibited prolonged sensitivity to burn injury, of a duration exceeding that observed in skeletal muscles or other lymphoid tissues.
Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, Boston, Massachusetts, USA.
S V
SV
Madihally
M
M
Toner
M L
ML
Yarmush
R N
RN
Mitchell
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D001830:Body Surface Area; D002056:Burns / Q000145:classification / Q000150:complications* / Q000378:metabolism*; D002470:Cell Survival; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005805:Genes, MHC Class I / Q000502:physiology*; D015601:Injury Severity Score; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008198:Lymph Nodes / Q000166:cytology; D016131:Lymphocyte Subsets; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000502:physiology; D009133:Muscular Atrophy / Q000209:etiology* / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology
D011506:Proteins