Published online before print August 11, 2006
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Department of Cell Biology and Molecular Genetics, University of Maryland, College Park
@ To whom correspondence should be addressed. E-mail: dmosser{at}umd.edu.
We generated three populations of macrophages (M
) in vitro and characterized each. Classically activated M (Ca-M) were primed with IFN-
and stimulated with LPS. Type II-activated M (M-II) were also similarly primed but stimulated with LPS plus immune complexes. Alternatively activated M (AA-M) were primed overnight with IL-4. Here, we present a side-by-side comparison of the three cell types but focus primarily on differences between M-II and AA-M, as both have been classified as M2 M, distinct from Ca-M. We show that M-II are more similar to Ca-M than they are to AA-M. M-II and Ca-M, but not AA-M, produce high levels of NO and have low arginase activity. AA-M express FIZZ1, whereas neither M-II nor Ca-M does. M-II and Ca-M express relatively high levels of CD86, whereas AA-M are virtually devoid of this costimulatory molecule. Ca-M and M-II are efficient APC, whereas AA-M fail to stimulate efficient T cell proliferation. The differences between Ca-M and M-II are more subtle. Ca-M produce IL-12 and give rise to Th1 cells, whereas M-II produce high levels of IL-10 and thus, give rise to Th2 cells secreting IL-4 and IL-10. M-II express two markers that may be used to identify them in tissue. These are sphingosine kinase-1 and homologous to lymphotoxins, shows inducible expression and competes with herpes simplex virus glycoprotein D for herpes virus entry mediator/TNF-related 2 (LIGHT; TNF superfamily 14), a member of the TNF superfamily. Thus, Ca-M, M-II, and AA-M represent three populations of cells with different biological functions.
Key Words: IL-10 • IL-12 • sphingosine kinase • LIGHT
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