PMID- 8955788
OWN - NLM
STAT- MEDLINE
DCOM- 19970515
LR  - 20131121
IS  - 0003-276X (Print)
IS  - 0003-276X (Linking)
VI  - 246
IP  - 4
DP  - 1996 Dec
TI  - Factors influencing fetal macrophage development: I. Reactions of the tumor 
      necrosis factor-alpha cascade and their inhibitors.
PG  - 481-97
AB  - BACKGROUND: When fetal rat lungs are explanted to organ culture, precursor 
      angular cells soon convert to nascent macrophages that multiply rapidly as they 
      mature into efficient phagocytes. The present study examines the influence of 
      proinflammatory early cytokines of the tumor necrosis factor-alpha (TNF alpha) 
      cascade on this initial expression of the macrophage phenotype. METHODS: 
      Fourteen- and 15-day fetal rat lungs were grown for varying periods on an 
      agar-solidified medium with and without test factors added singly or in 
      combination. Growth of the macrophage population was followed daily by light 
      microscopy and quantified by measuring the area of coronas formed as cells 
      emerged from explants. RESULTS: TNF alpha interleukin-1 beta (IL-1 beta) 
      stimulated growth of the macrophage population, as had macrophage- and 
      granulocyte-macrophage colony-stimulating factors (M- and GM-CSFs) in prior 
      studies. Inhibition was obtained by exposure to IL-1 receptor antagonist and 
      antibodies neutralizing the CSFs. Only the effects of TNF alpha were sufficiently 
      delayed to discount possible influence on conversion and growth of nascent 
      macrophages. Two transcription blockers, dexamethasone and pyrrolidine 
      dithiocarbamate (PDTC), an inhibitor of nuclear factor NF-kappa B, both 
      profoundly suppressed macrophage growth without preventing conversion of 
      precursors. Effects of dexamethasone were significantly ameliorated by IL-1 beta 
      alone and combined with GM-CSF; those of PDTC were mitigated by M-CSF and a 
      combination of IL-1 beta and TNF alpha but not by GM-CSF. CONCLUSIONS: IL-1 beta, 
      M-CSF, and GM-CSF all promote growth of the young macrophage population. TNF 
      alpha is effective only later on, likely because early-stage cells lack its 
      receptors which normally use intracellular signalling pathways similar to those 
      for IL-1. The severity of PDTC inhibition to population growth indicates that 
      NF-kappa B is important for transmitting proliferative signals in these cells.
FAU - Sorokin, S P
AU  - Sorokin SP
AD  - Department of Anatomy and Neurobiology, Boston, University School of Medicine, MA 
      02118-2394, USA.
FAU - Hoyt, R F Jr
AU  - Hoyt RF Jr
FAU - McNelly, N A
AU  - McNelly NA
LA  - eng
GR  - HL-33070/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Anat Rec
JT  - The Anatomical record
JID - 0370540
RN  - 0 (Interleukin-1)
RN  - 0 (Pyrrolidines)
RN  - 0 (Receptors, Interleukin-1)
RN  - 0 (Thiocarbamates)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 25769-03-3 (pyrrolidine dithiocarbamic acid)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - 81627-83-0 (Macrophage Colony-Stimulating Factor)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Animals
MH  - Cell Division/drug effects
MH  - Dexamethasone/pharmacology
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/antagonists & 
      inhibitors/pharmacology
MH  - Interleukin-1/pharmacology
MH  - Lung/drug effects/embryology/immunology
MH  - Macrophage Colony-Stimulating Factor/antagonists & inhibitors/pharmacology
MH  - Macrophages, Alveolar/drug effects/*physiology
MH  - Organ Culture Techniques
MH  - Pyrrolidines/pharmacology
MH  - Rats
MH  - Receptors, Interleukin-1/antagonists & inhibitors
MH  - Thiocarbamates/pharmacology
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 1996/12/01 00:00
MHDA- 2000/06/20 09:00
CRDT- 1996/12/01 00:00
PHST- 1996/12/01 00:00 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1996/12/01 00:00 [entrez]
AID - 10.1002/(SICI)1097-0185(199612)246:4<481::AID-AR8>3.0.CO;2-Y [pii]
AID - 10.1002/(SICI)1097-0185(199612)246:4<481::AID-AR8>3.0.CO;2-Y [doi]
PST - ppublish
SO  - Anat Rec. 1996 Dec;246(4):481-97. doi: 
      10.1002/(SICI)1097-0185(199612)246:4<481::AID-AR8>3.0.CO;2-Y.