Conservation of macrophage polarization in fish

Macrophages of higher vertebrates can express a range of activation states, with the extremes termed M1 and M2. Neither the evolutionary conservation of these activation states, nor the exact microbial and/or cytokine stimulants involved, have been examined in detail in lower vertebrates. We have shown that macrophages of teleost fish, including carp, have the ability to polarize into activation states typical of classical (M1) and alternative (M2) extremes upon stimulation with LPS, or exogenous cAMP, respectively. Upon this polarization, carp macrophages display functional profiles and several molecular markers that indicate the M1-M2 dichotomy could be an intrinsic property of macrophages which arose early in evolution. Owing to the more recent discoveries of IFN-y and lL-4/IL-13-like cytokines in teleost fish, we now can also study cytokine-dependent polarization of carp macrophages. Interferon-y amplifies LPS-induced polarisation into M1-like profiles of carp macrophages, including the induction of nitric oxide. Strikingly, IL-4/IL-13 appears to increase levels of arginase along with an activation profile that at least partly overlaps with that of cAMP-induced M2 macrophages. Thus, the chief macrophage M1 and M2 activation states appear to operate under the guidance of primordially conserved principles.