CD34-deficient mice have reduced eosinophil accumulation after allergen exposure and show a novel crossreactive 90-kD protein

Akira Suzuki, David P. Andrew, Jose Angel Gonzalo, Manabu Fukumoto, Jason Spellberg, Motohiro Hashiyama, Hiroaki Takimoto, Nicole Gerwin, Lain Webb, Graham Molineux, Ryuichi Amakawa, Yoshifumi Tada, Andrew Wakeham, John Brown, Ian McNiece, Klause Ley, Eugene C. Butcher, Toshio Suda, Jose Carlos Gutierrez-Ramos, Tak Wah Mak

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Abstract

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.

Original languageEnglish
Pages (from-to)3550-3562
Number of pages13
JournalBlood
Volume87
Issue number9
Publication statusPublished - 1996 May 1

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Venules
Eosinophils
Allergens
L-Selectin
Animals
Lymphocytes
Leukocyte Rolling
Wild Animals
Stem Cells
Lymph Nodes
Stromal Cells
Hematopoietic Stem Cells
Proteins
Molecules
Ovalbumin
Granulocyte Colony-Stimulating Factor
Stem cells
Fluorouracil
Lung
Peritoneum

ASJC Scopus subject areas

  • Hematology

Cite this

Suzuki, A., Andrew, D. P., Gonzalo, J. A., Fukumoto, M., Spellberg, J., Hashiyama, M., ... Mak, T. W. (1996). CD34-deficient mice have reduced eosinophil accumulation after allergen exposure and show a novel crossreactive 90-kD protein. Blood, 87(9), 3550-3562.

CD34-deficient mice have reduced eosinophil accumulation after allergen exposure and show a novel crossreactive 90-kD protein. / Suzuki, Akira; Andrew, David P.; Gonzalo, Jose Angel; Fukumoto, Manabu; Spellberg, Jason; Hashiyama, Motohiro; Takimoto, Hiroaki; Gerwin, Nicole; Webb, Lain; Molineux, Graham; Amakawa, Ryuichi; Tada, Yoshifumi; Wakeham, Andrew; Brown, John; McNiece, Ian; Ley, Klause; Butcher, Eugene C.; Suda, Toshio; Gutierrez-Ramos, Jose Carlos; Mak, Tak Wah.

In: Blood, Vol. 87, No. 9, 01.05.1996, p. 3550-3562.

Research output: Contribution to journalArticle

Suzuki, A, Andrew, DP, Gonzalo, JA, Fukumoto, M, Spellberg, J, Hashiyama, M, Takimoto, H, Gerwin, N, Webb, L, Molineux, G, Amakawa, R, Tada, Y, Wakeham, A, Brown, J, McNiece, I, Ley, K, Butcher, EC, Suda, T, Gutierrez-Ramos, JC & Mak, TW 1996, 'CD34-deficient mice have reduced eosinophil accumulation after allergen exposure and show a novel crossreactive 90-kD protein', Blood, vol. 87, no. 9, pp. 3550-3562.
Suzuki A, Andrew DP, Gonzalo JA, Fukumoto M, Spellberg J, Hashiyama M et al. CD34-deficient mice have reduced eosinophil accumulation after allergen exposure and show a novel crossreactive 90-kD protein. Blood. 1996 May 1;87(9):3550-3562.
Suzuki, Akira ; Andrew, David P. ; Gonzalo, Jose Angel ; Fukumoto, Manabu ; Spellberg, Jason ; Hashiyama, Motohiro ; Takimoto, Hiroaki ; Gerwin, Nicole ; Webb, Lain ; Molineux, Graham ; Amakawa, Ryuichi ; Tada, Yoshifumi ; Wakeham, Andrew ; Brown, John ; McNiece, Ian ; Ley, Klause ; Butcher, Eugene C. ; Suda, Toshio ; Gutierrez-Ramos, Jose Carlos ; Mak, Tak Wah. / CD34-deficient mice have reduced eosinophil accumulation after allergen exposure and show a novel crossreactive 90-kD protein. In: Blood. 1996 ; Vol. 87, No. 9. pp. 3550-3562.
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AU - Hashiyama, Motohiro

AU - Takimoto, Hiroaki

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AU - Molineux, Graham

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AU - Tada, Yoshifumi

AU - Wakeham, Andrew

AU - Brown, John

AU - McNiece, Ian

AU - Ley, Klause

AU - Butcher, Eugene C.

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AU - Gutierrez-Ramos, Jose Carlos

AU - Mak, Tak Wah

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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.

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