Cancer-induced expansion and activation of CD11b + Gr-1 + cells predispose mice to adenoviral-triggered anaphylactoid-type reactions

Kalyan Pande, Roanna Ueda, Todd Machemer, Manjiri Sathe, Van Tsai, Elena Brin, Matthew J. Delano, Nico Van Rooijen, Terrill K. McClanahan, James E Talmadge, Lyle L. Moldawer, Joseph H. Phillips, Drake M. LaFace

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Intravascular delivery (1.5 × 10 9 particles and higher) of recombinant adenovirus (rAd) induces myeloid cell mediated, self-limiting hemodynamic responses in normal mice. However, we observed anaphylactoid-type reactions and exacerbated hemodynamic events following rAd injection in mice bearing malignant 4T1 mammary carcinoma. Because 4T1 tumors induce significant CD11b + Gr-1 + myeloid cell expansion and activation, we set to determine whether this causes rAd-induced exaggerated responses. When treated with a single intravenous dose (1 × 10 10 particles) of rAd, mice implanted with 4T1 carcinoma succumbed due to the anaphylactoid-type reactions. In contrast, normal mice and mice implanted with a related mammary carcinoma (66cl4) that does not induce CD11b + Gr-1 + cell expansion, showed minimal responses. Depletion of phagocytic CD11b + Gr-1 + cells prior to rAd delivery protected 4T1 tumor-bearing animals, whereas passive transfer of CD11b + Gr-1 + cells from 4T1 tumor-bearing animals was sufficient to convey susceptibility to anaphylactoid-type reactions in normal animals. We further show that there is upregulation of nitric oxide and leukotriene signaling pathways in the 4T1 tumor-induced CD11b + Gr-1 + myeloid cells and that pretreating mice with inhibitors of nitric oxide synthetase and leukotrienes can attenuate the anaphylactoid-type reactions. These data show that malignant tumor growth can alter CD11b + Gr-1 + myeloid cells, rendering hosts susceptible to anaphylactoid-type reactions upon intravascular treatment with rAd.

Original languageEnglish (US)
Pages (from-to)508-515
Number of pages8
JournalMolecular Therapy
Volume17
Issue number3
DOIs
StatePublished - Jan 7 2009

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Adenoviridae
Myeloid Cells
Neoplasms
Leukotrienes
Hemodynamics
Breast Neoplasms
Nitric Oxide Synthase
Nitric Oxide
Up-Regulation
Carcinoma
Injections
Growth

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Cite this

Cancer-induced expansion and activation of CD11b + Gr-1 + cells predispose mice to adenoviral-triggered anaphylactoid-type reactions . / Pande, Kalyan; Ueda, Roanna; Machemer, Todd; Sathe, Manjiri; Tsai, Van; Brin, Elena; Delano, Matthew J.; Van Rooijen, Nico; McClanahan, Terrill K.; Talmadge, James E; Moldawer, Lyle L.; Phillips, Joseph H.; LaFace, Drake M.

In: Molecular Therapy, Vol. 17, No. 3, 07.01.2009, p. 508-515.

Research output: Contribution to journalArticle

Pande, K, Ueda, R, Machemer, T, Sathe, M, Tsai, V, Brin, E, Delano, MJ, Van Rooijen, N, McClanahan, TK, Talmadge, JE, Moldawer, LL, Phillips, JH & LaFace, DM 2009, ' Cancer-induced expansion and activation of CD11b + Gr-1 + cells predispose mice to adenoviral-triggered anaphylactoid-type reactions ', Molecular Therapy, vol. 17, no. 3, pp. 508-515. https://doi.org/10.1038/mt.2008.280
Pande, Kalyan ; Ueda, Roanna ; Machemer, Todd ; Sathe, Manjiri ; Tsai, Van ; Brin, Elena ; Delano, Matthew J. ; Van Rooijen, Nico ; McClanahan, Terrill K. ; Talmadge, James E ; Moldawer, Lyle L. ; Phillips, Joseph H. ; LaFace, Drake M. / Cancer-induced expansion and activation of CD11b + Gr-1 + cells predispose mice to adenoviral-triggered anaphylactoid-type reactions In: Molecular Therapy. 2009 ; Vol. 17, No. 3. pp. 508-515.
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AU - Tsai, Van

AU - Brin, Elena

AU - Delano, Matthew J.

AU - Van Rooijen, Nico

AU - McClanahan, Terrill K.

AU - Talmadge, James E

AU - Moldawer, Lyle L.

AU - Phillips, Joseph H.

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