Developmental Expression of Two CXC Chemokines, Mip-2 and Kc, and Their Receptors

Abstract

CXC chemokines, macrophage inflammatory protein-2 (MIP-2) and KC, (a cloning designation based on ordinate and abscissa position) as well as the CXC chemokine receptor, CXCR2, are expressed in a variety of cells and tissues in adult mice. Targeted deletion of the gene encoding murine CXCR2 does not result in obvious changes in the development of the organ system of the mouse, though the CXCR2 −/− mouse is compromised with regard to its ability to resist infection, heal wounds, and maintain homeostasis when challenged with microbes and/or chemicals. In an attempt to develop insight into additional possible subtle roles of CXCR2 and its ligands in the development of the mouse, we examined the expression of MIP-2, KC, CXCR2, as well as the Duffy antigen binding protein for chemokines during embryonic (p.c.) days 11.5 through 14.5 in the mouse. We observed strong correlation between the expression of MIP-2 and CXCR2 in the developing brain, cardiovascular system and condensing mesenchyme between 11.5 and 13.5 days. Moreover, the expression of KC was parallel to the expression of the Duffy antigen binding protein for chemokines with regard to temporal pattern and tissue localization. MIP-2 and CXCR2 are highly expressed in the brain, first in the cerebellum and in the head mesenchyme, the meninges and the floor plate, and by 14.5 days are also present in the telencephalon, thalamus and hypothalamus. In the developing brain KC and Duffy were prominently expressed in the neuronal tracts, the forebrain, sympathetic ganglia, and along the periphery of the neural tube. However, KC and Duffy were less prevalent in the developing cardiovascular system, lung and other organs, muscle and bone, than are CXCR2 and MIP-2. These data suggest that the roles for these chemokines and their receptors during development may be more significant than was initially thought based upon the phenotype of the mice with targeted deletion of CXCR2 and Duffy.

LeishmaniaPromastigotes Release a Granulocyte Chemotactic Factor and Induce Interleukin-8 Release but Inhibit Gamma Interferon-Inducible Protein 10 Production by Neutrophil Granulocytes

“…Indeed, studies in our laboratory revealed a rapid expression of KC and MIP-2 in the skin of mice infected with L. major (15). KC and MIP-2 are the functional homologues of IL-8 in mice (12).…”

The Duffy Antigen Modifies Systemic and Local Tissue Chemokine Responses following Lipopolysaccharide Stimulation

“…A sheep anti-murine Duffy polyclonal Ab was used at 1/50 dilution to immunolocalize Duffy Ag in WT lungs following total body irradiation. The verification of the murine Duffy Ab and method for Duffy immunostaining have been previously described (25). Amino-ethylcarbazole (red chromogen) was used as substrate for peroxidase.…”

“…We determined Duffy Ag expression in the lungs following total irradiation in WT mice using a murine Duffy-specific Ab (25). Immunoreactivity was present in the lung endothelium (Fig.…”

CXCL1 Inhibits Airway Smooth Muscle Cell Migration through the Decoy Receptor Duffy Antigen Receptor for Chemokines

“…DARC has been established as a promiscuous chemokine receptor that can bind several chemokines, including CXCL1, to which it binds with the highest affinity (27). The expression of KC (the mouse ortholog of human CXCL1) and DARC was found to follow parallel temporal patterns and tissue localization during mouse development (28), suggesting that a relationship may exist between the two. In general, DARC was found to maintain chemokine homeostasis in the blood (29) and to facilitate chemokine transcytosis and presentation across endothelium (30,31).…”