Cytokines differentially regulate complement receptor immunoglobulin (CRIg) in human macrophages: a control point in inflammation — ASN Events
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  3. Cytokines differentially regulate complement receptor immunoglobulin (CRIg) in human macrophages: a control point in inflammation

Cytokines differentially regulate complement receptor immunoglobulin (CRIg) in human macrophages: a control point in inflammation (#303)

Usma Munawara 1 2 3 , Kanchana Usuwanthim 1 2 4 , Yuefang Ma 1 , Alex Quach 1 2 , Nick Gorgani 1 2 , Charles Hii 1 2 , Catherine Abbott 3 , Antonio Ferrante 1 2 4 5 6
  1. Department of Immunopathology, SA Pathology at Women’s and Children’s Hospital, North Adelaide, South Australia
  2. School of Paediatrics and Reproductive Health, Robinson Research Institute, University of Adelaide, Adelaide
  3. School of Biological Sciences, Flinders University; Bedford Park, South Australia
  4. Department of Medical Technology, Faculty of Allied Health Sciences, Naresuan University, Thailand
  5. Discipline of Microbiology and Immunology, University of Adelaide , South Australia,
  6. School of Pharmacy and Medical Sciences, University of South Australia., South Australia.

Aim(s) and Introduction
CRIg, a recently characterized complement receptor, is structurally and functionally distinct from the classical complement receptors, CR3/CR4. CRIg expression is restricted to macrophages. While these receptors promote phagocytosis, CRIg also expresses anti-inflammatory/immunosuppressive activity. Reduced ratio of CRIg to CR3 expression in macrophages skews the response towards inflammation. We propose that CRIg is a control point in inflammation and its expression is regulated by cytokines in a manner that is commensurate with the action of the cytokines (that cytokine actions occur via regulating CRIg expression).

Methods
Cytokines were examined for their effects on (i) the differentiation of human monocytes to CRIg+ macrophages in culture, (ii) CRIg expression in monocyte-derived macrophages (MDM) and (iii) CRIg expression in dendritic cells (DC) generated from GM-CSF/IL-4 treated monocytes. The range of cytokines investigated included Th1, Th2, pyrogenic, regulatory and haematopoietic growth factors types (LT, IFN-γ, IL-4, IL-13, TNF-α, IL-1β, IL-6, IL-10, TGF-β1, M-CSF and GM-CSF). CRIg mRNA was measured by qRT-PCR and protein by Western blot and/or flow cytometry.

Results
Development of CRIg+ macrophages and CRIg expression in MDM and DC was positively or negatively regulated by cytokines. The changes caused by these cytokines were dependent on the macrophage type or process and conducive with their role in promoting or protecting against inflammation associated with rheumatoid arthritis and atherosclerosis. The cytokines similarly regulated both spliced forms of CRIg. The results also showed that the cytokines differentially regulated CR3/CR4 compared with CRIg expression. Furthermore, using PKCα-deficient MDM generated by RNAi, our data demonstrated that PKCα plays an important role in regulating CRIg expression in macrophages and that cytokines such as TNF-α regulated CRIg expression via PKCα.

Conclusions
Cytokines regulate the development of CRIg+ macrophages and CRIg expression on macrophages and DC, in a manner conducive with their role in inflammation.