Non-Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock


Introduction Rat Monocytes

Rats and mice are related species both belonging to the subfamily of Murinae. Still, looking at the immune system there can be substantial differences between the two. For the study of monocytes in the rat there are few limitations with respect to access and volume, but the number of available antibodies against informative cell surface markers for this species is low. Still, with monoclonal antibodies and flow cytometry, monocytes can be reliably identified via CD68 or CD172a and subsets can be determined with CD43 alone or combined with His48. Early on using CD172a on low scatter cells a CD43high and a CD43low subset was identified (Ahuja et al, Cellular Immunology, 163:59, 1995). The CD43high cells compared to the C43low cells were demonstrated to express higher CX3CR1 and lower CCR2 (Yrlid et al., J Immunol, 176: 4155, 2006) and the cells exclusively express CD16 transcripts (Turner Stokes et al, JASN, 31: 2523, 2020) suggesting that the CD43high cells are homologues of the human non-classical monocytes.

Studies in the rat model have shown that CD172a CD43hi non-classicals can develop form classical monocyte in vivo (Yrlid J Immunol, 176: 4155, 2006) confirming findings in mouse and man. Also CD43++ monocytes are depleted with M-CSF-R knock-out, while there is no change in CD43low cells (Keshvari et al, PLoS Genet 17(6):e1009605, 2021) a finding in line with data from patients with a heterozygous mutation of the M-CSF-R gene in man (Hofer et al, Blood,126: 2601, 2015). The rat is an excellent model for migration studies, in that for example, Turner Stokes et al have shown that CD43high non-classical monocytes survey the vasculature in the renal glomerulus without transmigration (Turner Stokes, JASN, 31: 2523, 2020)

While in man the non-classical subset accounts for 15% of all monocytes, in the rat this subset dominates at 60-80% of monocytes but this proportion reverses with IFNgamma infusion (Scriba et al, J Leuk Biol, 62: 741, 1997).