TY - JOUR
T1 - CD34-deficient mice have reduced eosinophil accumulation after allergen exposure and show a novel crossreactive 90-kD protein
AU - Suzuki, Akira
AU - Andrew, David P.
AU - Gonzalo, Jose Angel
AU - Fukumoto, Manabu
AU - Spellberg, Jason
AU - Hashiyama, Motohiro
AU - Takimoto, Hiroaki
AU - Gerwin, Nicole
AU - Webb, Lain
AU - Molineux, Graham
AU - Amakawa, Ryuichi
AU - Tada, Yoshifumi
AU - Wakeham, Andrew
AU - Brown, John
AU - McNiece, Ian
AU - Ley, Klause
AU - Butcher, Eugene C.
AU - Suda, Toshio
AU - Gutierrez-Ramos, Jose Carlos
AU - Mak, Tak Wah
PY - 1996/5/1
Y1 - 1996/5/1
N2 - CD34 is expressed on the surface of hematopoietic stem/progenitor cells, 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 (PLN). We generated CD34-deficient mutant animals through the use of homologous recombination. Wild-type and mutant animals showed no differences in lymphocyte binding to PLN HEV, in leukocyte rolling on venules or homing to PLN, in neutrophil extravasation into peritoneum in response to inflammatory stimulus, nor in delayed type hypersensitivity. Anti-L-selectin monoclonal antibody (MEL-14) also inhibited these immune responses similarly in both CD34-deficient and wild-type mice. However, eosinophil accumulation in the lung after inhalation of a model allergen, ovalbumin, is several-fold lower in mutant mice. We found no abnormalities in hematopoiesis in adult mice and interactions between mutant progenitor cells and a stromal cell line in vitro were normal. No differences existed in the recovery of progenitor cells after 5- fluorouracil treatment, nor in the mobilization of progenitor cells after granulocyte colony-stimulating factor treatment compared with wild-type animals. Surprisingly, although CD34 was not expressed in these mice, a portion of its 90-kD band crossreactive with MECA79 remained after Western blot. Thus, we have identified an additional molecule(s) that might be involved in leukocyte trafficking. These results indicate that CD34 plays an important role in eosinophil trafficking into the lung.
AB - CD34 is expressed on the surface of hematopoietic stem/progenitor cells, 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 (PLN). We generated CD34-deficient mutant animals through the use of homologous recombination. Wild-type and mutant animals showed no differences in lymphocyte binding to PLN HEV, in leukocyte rolling on venules or homing to PLN, in neutrophil extravasation into peritoneum in response to inflammatory stimulus, nor in delayed type hypersensitivity. Anti-L-selectin monoclonal antibody (MEL-14) also inhibited these immune responses similarly in both CD34-deficient and wild-type mice. However, eosinophil accumulation in the lung after inhalation of a model allergen, ovalbumin, is several-fold lower in mutant mice. We found no abnormalities in hematopoiesis in adult mice and interactions between mutant progenitor cells and a stromal cell line in vitro were normal. No differences existed in the recovery of progenitor cells after 5- fluorouracil treatment, nor in the mobilization of progenitor cells after granulocyte colony-stimulating factor treatment compared with wild-type animals. Surprisingly, although CD34 was not expressed in these mice, a portion of its 90-kD band crossreactive with MECA79 remained after Western blot. Thus, we have identified an additional molecule(s) that might be involved in leukocyte trafficking. These results indicate that CD34 plays an important role in eosinophil trafficking into the lung.
UR - http://www.scopus.com/inward/record.url?scp=15844403221&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=15844403221&partnerID=8YFLogxK
U2 - 10.1182/blood.v87.9.3550.bloodjournal8793550
DO - 10.1182/blood.v87.9.3550.bloodjournal8793550
M3 - Article
C2 - 8611677
AN - SCOPUS:15844403221
SN - 0006-4971
VL - 87
SP - 3550
EP - 3562
JO - Blood
JF - Blood
IS - 9
ER -