Developmental expression of two CXC chemokines, MIP-2 and KC, and their receptors

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. (C) 2001 Academic Press.