The CD11b promoter directs high-level expression of reporter genes in macrophages in transgenic mice [published erratum appears in Blood 1995 Apr 1;85(7):1983]

Abstract

CD11b is the alpha chain of the Mac-1 integrin and is preferentially expressed in myeloid cells (neutrophils, monocytes, and macrophages). We have previously shown that the CD11b promoter directs cell-type- specific expression in myeloid lines using transient transfection assays. To confirm that these promoter sequences contain the proper regulatory elements for correct myeloid expression of CD11b in vivo, we have used the -1.7-kb human CD11b promoter to direct reporter gene expression in transgenic mice. Stable founder lines were generated with two different reporter genes, a Thy 1.1 surface marker and the Escherichia coli lacZ (beta-galactosidase) gene. Analysis of founders generated with each reporter demonstrated that the CD11b promoter was capable of driving high levels of transgene expression in murine macrophages for the lifetime of the animals. Similar to the endogenous gene, transgene expression was preferentially found in mature monocytes, macrophages, and neutrophils and not in myeloid precursors. These experiments indicate that the -1.7 CD11b promoter contains the regulatory elements sufficient for high-level macrophage expression. This promoter should be useful for targeting heterologous gene expression to mature myeloid cells.

Immune modulation by MANF promotes tissue repair and regenerative success in the retina

“…The induction of PDGF-A was followed by a significant increase in MANF transcripts (Fig. 3C) and the detection of MANF + innate immune cells, identified by CD11b expression (45,46), in the vitreous (Fig. 3D and fig.…”

Promoter considerations in the design of lentiviral vectors for use in treating lysosomal storage diseases

“…After the introduction into the patient, cells first differentiate into macrophages, and in the brain, into myeloid cells. 75 In recent years, ex vivo lentiviral-mediated gene therapy with CD11b has been used in many LSDs, including MPS II, 76 IIIA, 77 , 78 IIIB, 79 all of which are characterized by damage to the central nervous system.…”

“…23 During the last decade, different promoters, including both tissue-specific and housekeeping, have been used to treat LSDs ( Figure 4 ).

Figure 4 Lentiviral vector promoters used in LSDs (based on 94 ) Promoters can be divided into two groups depending on their expression site: tissue-specific (CD11b; 75 , 119 ALB; 120 TBG; 72 MHC; 121 MLC2v; 122 , 123 cTnT; 124 , 125 ) or ubiquitous/housekeeping (CMV; 126 , 127 PGK; 27 , 127 , 128 EF-1α; 43 , 127 MND; 57 MCU3; 58 , 59 SFFV; 129 , 130 ; CBh; 131 ). If the recombinant gene product is to be secreted in all cell types, then housekeeping/ubiquitous promoters are preferable.

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Senolytic effects of exercise in human muscles require acute inflammation

“…Cellular senescence has been shown to increase proinflammatory myeloid differentiation for phagocytosis [8,9], characterized by increased CD11b mRNA of myeloid cells in tissues [10,11]. Inflammation is a local immune response that functions to recognize and clear senescent cells [12,13], followed by cell regeneration until inflammation is resolved [14].…”