Corticotropin‐Releasing Hormone Immunoreactivity in Human T and B Cells and Macrophages: Colocalization With Arginine Vasopressin

Abstract

Corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) are expressed in cells of the immune system where they exert immunomodulatory roles, but these neuropeptides are poorly characterized in human immune tissues. The aim of this study was to determine concentrations and distribution of CRH and AVP in nonactivated human peripheral blood mononuclear cells (PBMC). PBMC from normal human subjects were separated into enriched subpopulations of T and B cells and monocytes/macrophages by a magnetic bead/monoclonal antibody technique. CRH and AVP were measured in cell extracts by radioimmunoassay (RIA). CRH-immunoreactivity (ir) ranged 0.24-0.8 fmol/million cells (n = 6 subjects) in T cell extracts, 0.4-2.7 fmol/million cells (n = 4) in B cells and 0.63-2.16 fmol/million cells (n = 4) in macrophages. AVP-ir ranged 0.2-0.95 fmol/million cells in T cell extracts, <0.1-0.8 fmol/million cells in B cells and 0.14-3.19 fmol/million cells in macrophages. Reversed-phase high-performance liquid chromatography (HPLC) of T and B cell extracts revealed a peak of CRH-ir which coeluted with synthetic CRH-41; this peak was not present in macrophages. A second peak of CRH-ir which eluted in a more hydrophobic position was observed in extracts of T and B cells and macrophages. This unidentified form of CRH-ir is the predominant form of CRH-ir in nonactivated human PBMC. This is the first study to demonstrate that CRH-ir and AVP-ir are colocalized within human T cells, B cells and monocytes/macrophages. We have confirmed observations of a variant form of CRH-ir in human PBMC and show that this is the predominant form in macrophages and B cells whereas CRH-ir, which coelutes with CRH(1-41) on HPLC, is present in significant amounts only in T cells. These data also confirm that CRH-ir in human PBMC is not urocortin because the antiserum used in the CRH RIA does not bind to urocortin.

Vasopressin and Its Immune Effects in Septic Shock

“…Vasopressin is expressed in peripheral mononuclear cells including T cells, B cells and monocytes/macrophages [74] . Interestingly, it is co-localized with CRF in T cells, B cells and monocytes/macrophages [75] . Vasopressin is also found in human thymic epithelial cells [76] and in B cells of the spleen [77] .…”

Lipopolysaccharide Increases Plasma Levels of Corticotropin-Releasing Hormone in Rats

“…Corticotropin-releasing hormone (CRH) is mainly localized in the brain [1,2], and can also be detected in peripheral tissues including the gut [3,4,5] and immune cells and organs [6,7,8] in experimental animals and humans [9,10,11]. Although these tissues can be potential sources of circulating CRH, earlier studies have indicated that CRH levels are either nondetectable in rats or low in human plasma [12] as assessed by radioimmunoassay (RIA).…”

Corticotropin-releasing hormone downregulates IL-10 production by adaptive forkhead box protein 3–negative regulatory T cells in patients with atopic dermatitis

“…34,35 CRH, the central mediator of the stress hormone system, has additional peripheral roles in the gastrointestinal tract, cardiovascular system, and skin. 36 CRH also has immunoreactivity and other functions in T cells in human subjects, [37][38][39] but it has yet to be directly proved that human T cells express CRHRs. Thus we first confirmed that circulating T cells expressed CRHR1/ CRHR2 protein and mRNA and that infiltrated T cells in AD skin expressed CRHR1/CRHR2 protein.…”