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176 lines (139 loc) · 4.98 KB
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PROGRAM
INITIAL
constant LuSA = 500 ! cm^2 for mouse (RDDR, EPA)
!-------------------------------------------------------------------------
! Cytokines
! General notes:
! Monocyte recruitment is controlled by MCP3 - secreted by epithelial cells and monocytes
! Neutrophil recruitment is driven by GROA - secreted by epithelial cells, t-cells, monocytes, neutrophils, etc
! NK recruitment is driven by IL1B
! NK activation (?) is driven by IL18, which is a surrogate for IFN-alpha and IFN-beta
! IFNG enhanced macrophages and is secreted by NK-cells
! MCP-3
constant kgenMCP3 = 0.2
constant MAX_MCP3_Mono = 50
! GROA
constant kgenGROA = 0.05
constant P50_GROA_N = 800
! IL-18
constant kgenIL18 = 0.02
!IL-1b
constant kgenIL1b = 0.01
! IFNG
constant P50_IFNG_M = 100
!-----------------------------------------------------------------------------
! Cells
! Dentritic Cells
DC_SURFACE0 = 200533.58306804 + 227996.8762
constant kAreaDC_SURFACE = 4.2e-5
! ceh - why the 0.9?
kdegDC = 0.9*kdiffMonoDC*Mono0/DC0 ! must be in steady state
kmigDC_BLDtoSURFACE = 0.1*kdiffMonoDC*Mono0/DC_SURFACE0 ! Must be balanced in steady state
kmigDC_SURFACEtoLYMPH = 0.1*kdiffMonoDC*Mono0/DC_SURFACE0
kmigDCA_SURFACEtoLYMPH = 30*kmigDC_SURFACEtoLYMPH
constant P50_rhoP_DC_SURFACE = 1500
! ATII
!ATII_BLD0 = 2.81E+06
ATII_SURFACE0 = 2.81E+06
!constant kLysATII = 0
constant kPhATII = 0.3e-13
!constant kmigATII_BLDtoSURFACE = 0
!constant kmigATII_BLDtoSURFACE_inflammatory = 0
constant MAX_rhop_ATII = 1e3
!krecATII_BLD = 0
! Neutrophil
N0 = 6.26E+05
constant kAreaN = 1.8e-13 ! cm*cm/hr
constant kLysN = 10
constant kdegN = 0.02
constant kmigN_BLDtoSURFACE = 0
constant kmigN_BLDtoSURFACE_inflammatory = 0
constant krecN_BLD = 0.02 ! basal recruitment, replication/cell division
! Monocytes
MONO0 = 5.90E+05
MonoBlood0 = Mono0
MonoBloodTissue0 = Mono0
constant kAreaMono = 2e-15
constant kLysMono = 0
constant kdegMono = 0 ! Based on half-life
kdiffMonoM = 0.03 ! 1/time for a monoctye to differentiate into macrophage (t Mono/M)
kdiffMonoDC = 0.03 ! 1/time for a monoctye to differentiate into dendritic cell (t Mono/DC)
krecMonoBlood = 0.04 ! 1/time for a monocyte to migrate
constant kdegMonoBlood = 0
kmigMonoBlood = krecMonoBlood
constant kmigMonoBlood_inflammatory = 0.1 ! Increase in influx per MCP-1 or MCP-3
constant MAX_rhoP_Mono = 1e5
! Macrophage
M0 = 954907 + 763323.9498
constant kLysPM = 0
constant kdegM = 0
kmigM_BLDtoSURFACE = kdiffMonoM*Mono0/M0 ! Must be balanced in steady state
kmigMP_SURFACEtoLYMPH = 2*kmigM_BLDtoSURFACE
constant Mvel = 0.02 ! cm/hr (Stober et al., 1989)
constant MDiam = 15.0e-4 ! mac diameter (cm)
constant CHEMOI = 1e-8 ! chemotactic index (fit, unitless)
constant P50_rhoP_M = 3e3
constant P50Lys = 0
! Natural killer cell
NK0 = 340
constant krecNK = 0.005 ! basal recruitment, replication/cell division
constant krecNK_inflammatory = 0.03
constant kdegNK = 0.005
constant kdegNK_anti_inflammatory = 0.04
END ! INITIAL
DYNAMIC
ALGORITHM IALG = 5
NSTEPS NSTP = 10
MAXTERVAL MAXT = 1.0e9
MINTERVAL MINT = 1.0e-9
CINTERVAL CINT = 0.1
DERIVATIVE
INCLUDE 'csl_files/TBL_Hall.csl'
rhoP = P_experimental/LuSA ! surface density of pathogen (num/cm**2)
PTot = P + PM + PN !+ PDC
PperM = PM/M
!PperDC = PDC/DC
PperN = PN/N
!--------------------------------------------------------------------------
! Cytokines
!--------------------------------------------------------------------------
include 'csl_files/MCP3.csl'
include 'csl_files/GROA.csl'
include 'csl_files/IL18.csl'
include 'csl_files/IL1B.csl'
!--------------------------------------------------------------------------
! Cells
!--------------------------------------------------------------------------
include 'csl_files/ATII.csl'
include 'csl_files/DC.csl'
INCLUDE 'csl_files/M.csl'
INCLUDE 'csl_files/Mono.csl'
INCLUDE 'csl_files/N.csl'
!--------------------------------------------------------------------------
! Natural killer cells
! anti-inflamm is IL-10 here I think - ceh
AIC = 1 ! place-holder for anti-inflammatory cytokine (IL-10 released by CTL?)
RdeathNK = kdegNK*NK + kdegNK_anti_inflammatory*AIC/(P50_anti_inflammatory + AIC)*NK
RrecNK = krecNK*NK0 + krecNK_inflammatory*IL1B/(P50_IC_NK + IL1B)*NK
NK = integ(RrecNK - RdeathNK,NK0)
!--------------------------------------------------------------------------
! Pathogen
RPh = RPhM + RPhN !+ RPhDC !+ RPhAT2
RPKillNK = 0
RPKillCTL = 0
RPKill = RPKillNK + RPKillCTL
RRelease = 0!RRelM !+ RRelN
RP = - RPh - RPKill + RRelease
P = integ(RP,0)
END ! DERIVATIVE
! Add discrete events here as needed
! DISCRETE
! END
! code that is executed once at each communication interval goes here
CONSTANT TSTOP = 10.0
TERMT (T .GE. TSTOP, 'checked on communication interval: REACHED TSTOP')
END ! DYNAMIC
TERMINAL
! code that is executed once at the end of a simulation run goes here
END ! TERMINAL
END ! PROGRAM