13 kDalton13 kDalton

FourFour genesgenes withwith nucleotidenucleotide sequencesequence homologieshomologiescorrespondingcorresponding toto calcitonincalcitonin areare knownknown.. TheseThese genesgenes arearecollectivelycollectively calledcalled thethe ""calcitonincalcitonin genegene familyfamily",", butbut theythey dodo notnotallall produceproduce thethe peptidepeptide hormonehormone calcitonincalcitonin.. TheThe ""CALCCALC--11""genegene isis responsibleresponsible forfor thethe productionproduction ofof calcitonincalcitonin andand itsitsprecursorprecursor protein,protein, procalcitoninprocalcitonin.. ThisThis genegene maymay beberesponsibleresponsible forfor thethe generationgeneration ofof inflammatoryinflammatory inducedinduced PCTPCT..

TheThe CALCCALC--IIII genegene hashas aa similarsimilar structurestructure toto CALCCALC--I,I, butbutsequencesequence analysisanalysis indicatesindicates thatthat thethe synthesissynthesis ofof calcitonincalcitoninmRNAmRNA isis unlikelyunlikely codescodes onlyonly forfor aa precursorprecursor andand differsdiffers fromfromCGRPCGRP--II inin 33 aminoacids)aminoacids).. TheThe CALCCALC--IIIIII genegene isis aauntranscribeduntranscribed pseudogenepseudogene.. TheThe CALCCALC--IVIV genegene containscontains onlyonly33 exonsexons andand codescodes forfor amylinamylin (a(a functionalfunctional opponentopponent ofofinsulin)insulin)..

Tyroid (C cells)Tyroid (C cells)

L t ?L t ?Leucocytes?Leucocytes?

ProcalcitoninProcalcitonin

Liver (histiocytes)Liver (histiocytes)( y )( y )

P l i iP l i i (PCT)(PCT) ii 116116 ii ididProcalcitoninProcalcitonin (PCT)(PCT) isis aa 116116 aminoamino acidacidproteinprotein withwith aa sequencesequence identicalidentical toto thatthat ofofthethe prohormoneprohormone ofof calcitonincalcitonin ((3232 aminoaminoacids)acids) UnderUnder normalnormal metabolicmetabolic conditionsconditionsacids)acids).. UnderUnder normalnormal metabolicmetabolic conditions,conditions,hormonallyhormonally activeactive calcitonincalcitonin isis producedproduced andandsecretedsecreted inin thethe CC--cellscells ofof thethe thyroidthyroid glandglandafterafter specificspecific intracellularintracellular proteolyticproteolytic

InIn severesevere bacterialbacterial infectionsinfections andandsepsissepsis,, however,however, intactintact procalcitoninprocalcitonin isisafterafter specificspecific intracellularintracellular proteolyticproteolytic

processionprocession ofof thethe prohormoneprohormone procalcitoninprocalcitonin.. foundfound inin bloodblood.. CurrentCurrent researchresearchindicatesindicates thatthat thethe orginorgin ofof procalcitoninprocalcitonininin thesethese conditionsconditions isis extrathyroidalextrathyroidal..

Increase of plasma and tissue Increase of plasma and tissue content in content in sepsissepsis..pp

The large degree of conservation of the gene in various species The large degree of conservation of the gene in various species indicates that it may have biologically important functions…indicates that it may have biologically important functions…

VariousVarious groupsgroups havehave attemptedattempted totouncoveruncover specificspecific biologicalbiological functionsfunctions ofofPCTPCT especiallyespecially immunologicimmunologic functionsfunctionsPCT,PCT, especiallyespecially immunologicimmunologic functionsfunctions..•• PCTPCT hashas somesome effecteffect onon plasmaplasma calciumcalcium levelslevels•• PCTPCT maymay functionfunction asas aa coco--factorfactor capablecapable ofof modulatingmodulating variousvarious effectseffectsCC ayay u ct ou ct o asas aa coco actoacto capab ecapab e oo odu at godu at g a ousa ous e ectse ects

duringduring endotoxinendotoxin shockshock•• InIn vitrovitro experimentsexperiments havehave shownshown thatthat itit hashas aa weakweak influenceinfluence onon

cytokinecytokine expressionexpression•• LowLow oror moderatelymoderately elevatedelevated PCTPCT concentrationsconcentrations significantlysignificantly

suppressedsuppressed TNFTNF--αα andand IFNIFN--γγ--stimulatedstimulated productionproduction ofof cDNAcDNA ofof iNOSiNOS ininsuppressedsuppressed TNFTNF αα andand IFNIFN γγ stimulatedstimulated productionproduction ofof cDNAcDNA ofof iNOSiNOS ininsmoothsmooth musclemuscle cells,cells, butbut notnot highhigh concentrationsconcentrations..

TT ff tt ff thth l it il it i f ilf il l it il it i•• TwoTwo groupsgroups ofof receptorsreceptors ofof thethe calcitonincalcitonin genegene family,family, calcitonincalcitoninreceptorsreceptors (CR)(CR) andand calcitonincalcitonin receptorreceptor--likelike receptorsreceptors (CRLR),(CRLR),

ll ll ii di tidi ti PCTPCT l t dl t d f tif timaymay playplay aa rolerole inin mediatingmediating PCTPCT--relatedrelated functionsfunctions..

•• MolecolaMolecola stabilestabile (in(in vivovivo tt11//22 2424 ore)ore)

•• InIn seguitoseguito aa stimolostimolo raggiungeraggiunge ilil piccopicco inin 33--44 oreore

eded ilil plateauplateau inin 66--1212 oreore

•• DopoDopo lala finefine dellodello stimolostimolo persistepersiste inin circolocircolo

perper circacirca 2424 oreoreperper circacirca 2424 oreore

•• NonNon sonosono richiestirichiesti particolariparticolari accorgimentiaccorgimenti perper ilil prelievoprelievo ee lalaconservazioneconservazione deldel campionecampioneco se a o eco se a o e dede ca p o eca p o e

•• II valorivalori didi PCTPCT sonosono fisiologicamentefisiologicamente aumentatiaumentati neinei primiprimi dueduegiornigiorni didi vitavitagg

CATABOLISMCATABOLISM

•• Like other plasma proteins, Like other plasma proteins, PCTPCT is probably is probably degraded by degraded by

proteolysisproteolysis..p yp y

•• Renal excretionRenal excretion of PCT plays a minor role. Clinical data have of PCT plays a minor role. Clinical data have

shown that PCT does not accumulate in cases of severe renalshown that PCT does not accumulate in cases of severe renalshown that PCT does not accumulate in cases of severe renal shown that PCT does not accumulate in cases of severe renal

dysfunction. The fall in plasma PCT concentrations observed in dysfunction. The fall in plasma PCT concentrations observed in

patients with renal dysfunction does not differ significantly from thatpatients with renal dysfunction does not differ significantly from thatpatients with renal dysfunction does not differ significantly from that patients with renal dysfunction does not differ significantly from that

of subjects with normal renal function.of subjects with normal renal function.

Dosaggio immunoluminometrico (ILMA) Dosaggio immunoluminometrico (ILMA) -- LUMItestPCTLUMItestPCTgg ( )gg ( )

The stability of PCT in blood samplesThe stability of PCT in blood samplesThe stability of PCT in blood samplesThe stability of PCT in blood samples-- Unlike most cytokines, Unlike most cytokines, PCT is highly stablePCT is highly stable in collected blood samples.in collected blood samples.-- In vitro plasma PCT concentrations fall by approximately In vitro plasma PCT concentrations fall by approximately 12% at room temperature12% at room temperature

d bd b 6% t t t f 4C6% t t t f 4C ft 24ft 24 hhand by and by 6% at a temperature of 4C6% at a temperature of 4C after 24after 24--hr.hr.-- PCT can be collected PCT can be collected with routine laboratory specimenswith routine laboratory specimens..-- The samples should be The samples should be stored in a refrigeratorstored in a refrigerator or, if storage or transport times are or, if storage or transport times are prolonged or if any additional influence on the samples is to be avoided during the prolonged or if any additional influence on the samples is to be avoided during the scope of the studies being implemented, scope of the studies being implemented, deep frozen until required for analysisdeep frozen until required for analysis..-- Both theBoth the type of anticoagulation and the use of plasma or serumtype of anticoagulation and the use of plasma or serum have no effect onhave no effect onBoth the Both the type of anticoagulation and the use of plasma or serumtype of anticoagulation and the use of plasma or serum have no effect on have no effect on PCT measurements.PCT measurements.-- However, a standardized collection technique, anticoagulation process and storage However, a standardized collection technique, anticoagulation process and storage procedures should be used for each hospital in order to minimize any discrepancy inprocedures should be used for each hospital in order to minimize any discrepancy inprocedures should be used for each hospital in order to minimize any discrepancy in procedures should be used for each hospital in order to minimize any discrepancy in the values obtained.the values obtained.