CD34+ progenitors have been found to possess receptors for various chemokines, and certain chemokines have been reported to have effects on in vitro hematopoiesis as measured by various progenitor assays. In order to further examine the role that chemokines might have on influencing the activation, proliferation, and function of CD34' progenitors, we have studied the effects of various C-C C-X-C, and CX3C chemokines on calcium ( Ca++ ) flux and cell transmigration. CD34+ cells show a Ca++ uptake response within 10 minutes in response to exposure to various chemokines as measured by lndo-1 Calcium fluorescence signal by confocal microscopy. As shown in the graph below, most chemokines resulted in Ca" response in bone marrow CD34+ cells, with Interleukm-8 (IL-8) and interferon gamma inducible protein-10 (IP-tO) showing significantly less response despite the presence of lnterleukin-8 receptor alpha and beta on CD34+ cells. Blood CD34+ cells demonstrate Ca" uptake and transendothelial migration in response to chemokines of a similar magnitude as marrow CD34+ cells. A higher percentage of early (CD34+/CD38-, CD34+/Thy-1+) subsets of CD34+ populations demonstrate Ca++ flux in response to chemokines as compared with CD34+/CD38+ cells. These studies demonstrate the ability of multiple chemokines of all classes to affect CD34+ cell activation as measured by Ca++ flux. Such réponses point to the possible importance of chemokine influence on early progenitor cell activation, mobility, and proliferation.
|Number of pages||1|
|State||Published - Dec 1 1998|