CD34-DEFICIENT MICE HAVE REDUCED EOSINOPHIL ACCUMULATION AFTER ALLERGEN EXPOSURE AND SHOW A NOVEL CROSS-REACTIVE 90-KD PROTEIN

CD34 is expressed on the surface of hematopoietic stem/progentior cell s, stromal cells, and on the surface of high-endothelial venules (HEV) . CD34 binds L-selectin, an adhesion molecule important for leukocyte rolling on venules and lymphocyte homing to peripheral lymph nodes (PL N). We generated CD34-deficient mutant animals through the use of homo logous recombination. Wild-type and mutant animals showed no differenc es in lymphocyte binding to PLN HEV, in leukocyte rolling on venules o r homing to PLN, in neutrophil extravasation into peritoneum in respon se to inflammatory stimulus, nor in delayed type hypersensitivity. Ant i-L-selectin monoclonal antibody (MEL-14) also inhibited these immune responses similarly in both CD34-deficient and wildtype mice. However, eosinophil accumulation in the lung after inhalation of a model aller gen, ovalbumin, is several-fold lower in mutant mice. We found no abno rmalities in hematopoiesis in adult mice and interactions between muta nt progenitor cells and a stromal cell line in vitro were normal. No d ifferences existed in the recovery of progenitor cells after 5-fluorou racil treatment, nor in the mobilization of progenitor cells after gra nulocyte colony-stimulating factor treatment compared with wild-type a nimals. Surprisingly, although CD34 was not expressed in these mice, a portion of its 90-kD band crossreactive with MECA79 remained after We stern blot. Thus, we have identified an additional molecule(s) that mi ght be involved in leukocyte trafficking. These results indicate that CD34 plays an important role in eosinophil trafficking into the lung. (C) 1996 by The American Society of Hematology.