M-1/M-2 macrophages and the Th1/Th2 paradigm

CD Mills, K Kincaid, JM Alt, MJ Heilman… - The Journal of …, 2000 - journals.aai.org
CD Mills, K Kincaid, JM Alt, MJ Heilman, AM Hill
The Journal of immunology, 2000journals.aai.org
Evidence is provided that macrophages can make M-1 or M-2 responses. The concept of M-
1/M-2 fomented from observations that macrophages from prototypical Th1 strains (C57BL/6,
B10D2) are more easily activated to produce NO with either IFN-γ or LPS than macrophages
from Th2 strains (BALB/c, DBA/2). In marked contrast, LPS stimulates Th2, but not Th1,
macrophages to increase arginine metabolism to ornithine. Thus, M-1/M-2 does not simply
describe activated or unactivated macrophages, but cells expressing distinct metabolic …
Abstract
Evidence is provided that macrophages can make M-1 or M-2 responses. The concept of M-1/M-2 fomented from observations that macrophages from prototypical Th1 strains (C57BL/6, B10D2) are more easily activated to produce NO with either IFN-γ or LPS than macrophages from Th2 strains (BALB/c, DBA/2). In marked contrast, LPS stimulates Th2, but not Th1, macrophages to increase arginine metabolism to ornithine. Thus, M-1/M-2 does not simply describe activated or unactivated macrophages, but cells expressing distinct metabolic programs. Because NO inhibits cell division, while ornithine can stimulate cell division (via polyamines), these results also indicate that M-1 and M-2 responses can influence inflammatory reactions in opposite ways. Macrophage TGF-β1, which inhibits inducible NO synthase and stimulates arginase, appears to play an important role in regulating the balance between M-1 and M-2. M-1/M-2 phenotypes are independent of T or B lymphocytes because C57BL/6 and BALB/c NUDE or SCID macrophages also exhibit M-1/M-2. Indeed, M-1/M-2 proclivities are magnified in NUDE and SCID mice. Finally, C57BL/6 SCID macrophages cause CB6F 1 lymphocytes to increase IFN-γ production, while BALB/c SCID macrophages increase TGF-β production. Together, the results indicate that M-1-or M-2-dominant macrophage responses can influence whether Th1/Th2 or other types of inflammatory responses occur.
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