Skeletal Muscle Produces Acute Phase Proteins in Response to Polymicrobial Sepsis

Abstract

Skeletal muscle has been implicated as an endocrine organ, as observed by the secretion of cytokines in response to multiple stimuli such as exercise, heat stress and infection. However, whether skeletal muscles can produce acute phase proteins (APPs) in response to polymicrobial sepsis is controversial. This is relevant since APPs play an important role in the transition from innate to adaptive immunity and, thus far, the liver has been considered the primary source of these proteins. Our aim was to determine whether skeletal muscles are capable of producing APPs in response to polymicrobial sepsis.METHODSWe injected (IP) 37 female C57BL/6J mice with cecal slurry (1.6 g/ml) and harvested the soleus, gastrocnemius and livers at 6, 12, and 24 h after the injection. Respective muscles and livers from non‐septic mice were used as controls. Specimens were then homogenized and analyzed for protein content. Immunoblot assays were then conducted using polyclonal antibodies for, serum amyloid a1 (SAA1), fibrinogen, lipocalin, and c‐reactive protein (CRP). For quantification, membranes were scanned for fluorescence intensity and normalized for total protein.RESULTSWe observed elevated expression of fibrinogen, lipocalin and SAA1 in the livers of septic mice across all time points in comparison to non‐septic mice. We observed an increased signal for SAA1 and fibrinogen in skeletal muscle of septic mice. Notably, the signal intensity was higher in soleus in comparison to gastrocnemius muscle, which suggests a muscle‐specific response. We did not observe any signal for lipocalin, regardless of the muscle type. We also detected the presence of CRP in the soleus muscles of septic mice. Our results suggest that the cecal slurry model of septic shock induces an acute phase response in both liver and skeletal muscle. Though skeletal muscles produce a smaller spectrum of known APPs, these may contribute to the transition from innate to adaptive immunity, and the overall response to severe bacterial infection.Support or Funding InformationSupported by NIH RO1GM118895‐01 and the BK and Betty Stevens Endowment.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.