Macrophages follow two major activation pathways, classical and alternative, according to the activating signals they receive.
Classical activation: M1 macrophages
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Classical activation is induced by microbial products such as endotoxin acting through TLRs and other sensors, and by T-cell mediators, especially IFN-g.
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M1 macrophages produce NO and ROS and increase lysosomal enzymes, enhancing their ability to kill ingested organisms.
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They secrete cytokines that stimulate inflammation, contribute to eradication of infections, and dominate many inflammatory reactions.
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Activated macrophages can also injure normal tissues.
Alternative activation: M2 macrophages
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Alternative activation is induced by mediators other than IFN-g, including IL-4 and IL-13 produced by T lymphocytes and other cells.
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M2 macrophages are not actively microbicidal; their principal function is tissue repair.
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They secrete growth factors that promote angiogenesis, activate fibroblasts, and stimulate collagen synthesis.
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M2 macrophages also inhibit inflammation.
Proposed sequence
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The passage proposes that classical activation may occur first to destroy offending agents and may subsequently be followed by alternative activation.