Update on the role of alternatively activated macrophages in asthma

Figures & data

Figure 1 Schematic diagram of subtypes of lung macrophages during allergic immune responses after exposure to allergen.

Notes: Exposure to allergens activates lung epithelial cells and other innate immune cells. The activated cells release a variety of cytokines and distinctly affect AM polarization and migration. Classically activated macrophages (M1 cells) can be activated by IFN-γ and LPS, inducing nonallergic immune responses through releasing TNF-α and IL-1 β. Alternatively, activated macrophages (M2 cells) are divided into M2a and M2c cells. M2a cells can be activated by IL-4, IL-13, and IL-33, inducing allergic immune responses through releasing IL-4 and IL-13. M2c cells can be activated by IL-10 and TGF-β, inducing lung inflammation resolution and tissue repair through releasing IL-10. Bone marrow-derived stromal cells and regulatory T cells also drive M2c cell polarization through IDO and IL-10. M2c cells have low activation markers and are more potent in phagocytosis of invading pathogens than other macrophage phenotypes.
Abbreviations: AM, alveolar macrophage; LPS, lipopolysaccharide; IDO, indoleamine 2,3-dioxygenase.

Table 1 Characteristics and molecular release from activated macrophages

Subtypes	Inducers	Cell markers	Cytokines	Chemokines	Function
M1	IFN-γ, LPS, bacteria GM-CSF, oxidative fatty acid/LDL, HMGB1	CCR7, CD25, CD86, CD127, MHCII, ROS, iNOS, arginase-2	TNF-α, IL-1 β, NO, IP-10, IL-6/8/12/15/17/23	RANTES, CCL-8/15/19/20, CXCL-9/10/11/13	Proinflammatory function Pathogen clearance, tissue damage
M2a	IL-4, IL-13, M-CSF, NLRP3	CD206, CD209, Fizzl, Ym1/2, RELM-α, arginase-1	IL-4/10/13/33/35, MMP-9, MMP-14, IGF-1	CCL-8/13/14, CCL-17/18/23/26	Allergic inflammation
M2b	LPS, IL-1 β, immune complex/IL-1Ra	CD206, CD209, Fizzl, Ym1/2, RELM-α, arginase-1	IL-10, TGF-β, CCL-1/20, CXCL-1/2/3	CCL-1/20, CXCL 1/2/3	Tissue remodeling, fibrosis
M2c	TGF-β, IL-10, PGE2, Tregs, BM-MSC, ADSCs, IDO	CD163, CD206, Fizzl, Ym1/2, arginase-1, PPAR-delta, SRA-1 TLR1/8	IL-10, TGF-β, IGF-1, PGE-2	CCL-8/17/18/22/24	Anti-inflammatory function Phagocytosis, tissue remodeling, fibrosis

Notes: M1 cells are classically activated macrophages; alternatively activated macrophages (M2 cells) can be divided into subtypes of M2a, M2b, and M2c.

Abbreviations: LPS, lipopolysaccharide; GM-CSF, granulocyte-macrophage colony-stimulating factor; LDL, low-density lipoprotein; HMGB1, high-mobility group box 1; iNOS, inducible nitric oxide synthase; Tregs, regulatory T cells; ADSCs, adipose tissue-derived stromal cells; IDO, indoleamine 2,3-dioxygenase; PPAR, peroxisome proliferator-activated receptor; SRA-1, scavenger receptor A-1; PGE2, prostaglandin E2.