Pre-mobilisation of neutrophils from acute exercise-induced muscle damage: potential implications for short-term vaccination responses, satellite cell dynamics and skeletal muscle recovery

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dc.contributor.advisorMyburgh, Kathryn H.en_ZA
dc.contributor.advisorDe Villiers, Carinen_ZA
dc.contributor.authorRawlins, Maiaen_ZA
dc.contributor.otherStellenbosch University. Faculty of Science. Dept. of Physiological Sciences.en_ZA
dc.date2023-02-27T12:37:23Z
dc.date2023-08-30T13:11:04Z
dc.date2023-02-27
dc.date.accessioned2023-02-27T12:37:23Z
dc.date.accessioned2023-08-31T09:18:31Z
dc.date.available2023-02-27T12:37:23Z
dc.date.available2023-08-31T09:18:31Z
dc.date.issued2023-03
dc.descriptionThesis (MSc)--Stellenbosch University, 2023. en_ZA
dc.description.abstractENGLISH ABSTRACT: Neutrophils are essential for both innate and adaptive immune responses. Exercise induced muscle damage (EIMD) elicits a rapid neutrophil response both systemically and infiltrate intramuscularly. Satellite cells (SCs) proliferate in response to EIMD with mechanisms related to local and systemic communication from cytokines or infiltrating immune cells. Hypothesis: i) COVID-19 vaccination will affect SCs and indirect markers of EIMD. ii) Plyometric exercise performed 24 hours before vaccination will augment immune responses to vaccination, in part by pre-mobilisation and activation of neutrophils. iii) Vaccination alone will affect SCs, neutrophil infiltration, and indirect measures of muscle damage. Twelve healthy male participants (21±3 yr.) were allocated into two groups. Twenty-four hours before receiving their third dose of Pfizer BioNTech COVID-19 vaccination, n = 8 performed 100 reps of plyometric drop-jumping exercise (EXG), n = 4 were non-exercising controls (CG). Four vastus lateralis muscle biopsies and eleven blood samples from the antecubital vein were taken before exercise (BL) and a time-course post-exercise and post- vaccination. Creatine kinase (CK), perceived muscle pain (PMP), maximal voluntary isometric force (MVIF) and isometric endurance time (IET) were assessed. Differential leukocyte counts and enzyme-linked immunosorbent assays for neutrophil activation markers: plasma myeloperoxidase (MPO), neutrophil elastase (NE) and the cytokine interleukin-6 (IL-6) were performed. Muscle neutrophil (CD11b⁺/MPO⁺) and SC pool (Pax7⁺) counts were determined by immunohistochemistry. Post-vacc side-effects were monitored by self-reporting questionnaires. CK peaked 27h post-exercise (1018±637 IU/L). PMP increased 7.5-fold at 24h post-ex and remained elevated until 48h post-vacc. MVIF reduced 16.6% and 13.0%, 24h-ex and 48h post-vacc respectively in EXG. CG had no significant changes in these parameters at any timepoint, even post-vacc. Neutrophil counts increased at 1h (p <0.05) and 2h (p<0.05) post-ex. Change in neutrophil counts and IL-6 at 2h post-ex tended to correlate (p=0.068). EXG had greater neutrophil counts at 1h and 2h post-vaccination vs CG (p<0.05). Both EXG and CG increased neutrophil counts at 24h post-vacc (p<0.05). Area under the curve for neutrophil counts (0-24h post-vacc) revealed EXG had greater neutrophil presence vs CG post-vacc (p<0.05). NE increased at 0.5h, 1h and 2h post-ex in EXG (p<0.05). Both groups increased NE 24h post-vacc (p<0.05). MPO increased 1h and 2h post-ex in EXG (p<0.05). In response to vacc, EXG increased MPO at 1h, 2h, 24h and 48h (p<0.05). CG had MPO increase at 48h post-vacc only (p<0.05). IL-6 was increased 2h post-ex in EXG (p<0.05), with no significant increase in either group 2h post-vacc. Neutrophil infiltration increased 24h post-ex and 48h post-ex in EXG (p<0.05). Neutrophil infiltration tended to increase 48h post-vacc in CG (p=0.069). SCs did not change at any timepoint in either group. There was a positive correlation between neutrophils and SCs 48h post-vacc in EXG (p=0.02). This relationship is absent at BL and 14 days post-vacc. Acute EIMD-induced pre-mobilisation of neutrophils resulted in a more profound acute neutrophil response to vaccination, which may explain some of the muscle aches and pains commonly reported post-vaccination. This may be pertinent given the premise that neutrophils play an important role in acute vaccination responses.en_ZA
dc.description.abstractAFRIKAANSE OPSOMMING: Neutrofiele is noodsaaklik vir beide aangebore asook aangepaste immuunreaksies. Oefening geïnduseerde spierbeskadiging (EIMD) ontlok akute sistemiese neutrofiel reaksies sowel as intramuskulêre infiltrasie. Satelliet- selle (SCs) prolifereer in reaksie op EIMD met meganismes wat verband hou met lokale en sistemiese kommunikasie vanaf sitokiene of infiltrerende immuunselle. Hipotese: i) COVID-19 inenting sal SCs en indirekte merkers van EIMD affekteer. ii) Pliometriese oefening 24h voor inenting sal die immuunrespons aanvul, deels deur pre-mobilisasie van neutrofiele. iii) Inenting alleenlik sal SCs, neutrofiel infiltrasie en indirekte merkers van spierskade affekteer. Twaalf gesonde manlike kandidate (21±3 jaar) was in twee eksperimentele groepe opgedeel. Vier-en-twintig uur voor ontvangs van hul derde dosis van die Pfizer BioNTech COVID-19 entstof (vacc), het n = 8 ’n reeks van 100 pliometriese valsprong oefeninge uitgevoer (EXG), n = 4 was die geen-oefening kontrole groep (CG). Vier spierbiopsies en elf bloedmonsters was voor-oefening (BL) en met ’n tydsverloop na-oefening en na-inenting geneem. Kreatien kinase (CK), spierpyn (PMP), maksimum isometriese krag (MVIF) en isometriese uithouvermoë-tyd (IET) was geassesseer. Differensiële leukosiettellings en ensiemgekoppelde immunosorberende toetse vir neutrofiel aktiveringsmerkers: myeloperoksidase (MPO), neutrofiel elastase (NE) en die sitokien interleukien-6 (IL-6) was uitgevoer. Spier neutrofiel (CD11b⁺/MPO⁺) en SC (Pax7⁺) tellings was deur immunohistochemie bepaal. CK het ’n maksimum bereik teen 27h na-oefening (1018.8±637.8 IU/L). PMP het 7.5-maal toegeneem teen 24h na-oefening en het verhewe gebly tot 48h na-inenting. MVIF het afgeneem met 16.6% teen 24h na-oefening en 13.0% teen 48h na-inenting in EXG. CG het geen beduidende veranderinge in hierdie parameters, selfs na-inenting, getoon nie. Neutrofiel tellings het toegeneem 1h (p<0.05) en 2h (p<0.05) na-oefening. Daar was ’n korrelasie in die tendens van verandering in neutrofiel tellings en IL-6 teen 2h na-oefening (p=0.068). EXG het hoër neutrofiel tellings teen 1h en 2h na-inenting gehad teenoor CG (p<0.05). Beide EXG en CG het ’n toename in neutrofiel tellings teen 24h na-inenting getoon (p<0.05). Oppervlakte onder die kurwe vir neutrofiel tellings (0-24h na- inenting) het gewys dat EXG ’n groter neutrofiel teenwoordigheid het teenoor CG na-inenting (p<0.05). NE het toegeneem teen 0.5h, 1h en 2h na-oefening in EXG (p<0.05). Beide groepe het ’n toename in NE 24h na-inenting (p<0.05) getoon. MPO het toegeneem 1h en 2h na-oefening in EXG (p<0.05). EXG het ’n toename in MPO ondervind teen 1h, 2h, 24h en 48h na-inenting (p<0.05). CG het ’n MPO toename op 48h na-inenting getoon (p<0.05). IL-6 was verhoog 2h na-oefening in EXG (p<0.05), met geen beduidende toename in enige groep 2h na- inenting nie. Neutrofiel infiltrasie het toegeneem 24h na-oefening en 48h na-oefening in EXG (p<0.05). Daar was ’n tendens tot toenemende neutrofiel infiltrasie 48h na-inenting in CG (p=0.069). SCs het geen verandering vir enige groep getoon nie. Daar was ’n positiewe korrelasie tussen neutrofiele en SCs 48h na-inenting in EXG (p=0.02). Akute EIMD-geïnduseerde pre-mobilisasie van neutrofiele het ‘n meer diepgaande akute neutrofiel respons tot inenting tot gevolg gehad, wat van die algemene spierpyne wat na inenting gerapporteer word kan verklaar. Dit mag betekenisvol wees in lig van die uitgangspunt dat neutrofiele ’n belangrike rol speel in akute inentingsrespons.af_ZA
dc.description.versionMastersen_ZA
dc.embargo.terms2023-12-01
dc.formatapplication/pdf
dc.format.extent223 pages : illustrationsen_ZA
dc.identifier.urihttps://scholar.sun.ac.za/handle/10019.1/128371
dc.languageen_ZAen_ZA
dc.publisherStellenbosch : Stellenbosch Universityen_ZA
dc.rights.holderStellenbosch Universityen_ZA
dc.subject.lcshMusculoskeletal systemen_ZA
dc.subject.lcshNeutrophilsen_ZA
dc.subject.lcshInflammation -- Chemotherapyen_ZA
dc.subject.lcshSatellite cells -- Effect of drugs onen_ZA
dc.subject.lcshCOVID-19 vaccinesen_ZA
dc.subject.lcshExercise induced muscle damage -- Treatmenten_ZA
dc.subject.lcshCOVID-19 (Disease) -- Vaccinationen_ZA
dc.subject.nameUCTDen_ZA
dc.titlePre-mobilisation of neutrophils from acute exercise-induced muscle damage: potential implications for short-term vaccination responses, satellite cell dynamics and skeletal muscle recoveryen_ZA
dc.typeThesisen_ZA
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