Transient gene transfer of non-ELR chemokines to rodent lung induces mononuclear cell accumulation and activation.
The in vivo function of the CXC chemokines interferon-inducible protein-10 (IP-10) and monokine induced by gamma (MIG) was examined using replication-deficient adenoviral vectors expressing human IP-10 (AdIP-10) or murine MIG (AdMIG). Intratracheal and intranasal administration of AdIP-10 or AdMIG into rats and mice produced transient chemokine overexpression from the bronchial epithelium. IP-10 concentrations in the bronchoalveolar lavage fluid (BAL) of AdIP-10-treated animals showed peak expression (>2 ng/ml) 24-48 h after AdIP-10 administration. Dramatic transient increases in BAL cellularity (macrophages, monocytes, lymphocytes, and neutrophils) were observed in AdIP-10-treated and AdMIG-treated animals, and histologic examination of AdIP-10-treated lungs revealed transient infiltrations of mononuclear cells primarily localized around the bronchus and extending throughout the lung parenchyma. However, in immunocomprised SCID mice, only increases in natural killer cell populations were detected in BAL following AdIP-10 intranasal administration, indicating that monocyte/macrophage and neutrophil accumulation was likely the result of factors released from activated lymphocytes.
Palmer
K
K
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Emtage
P C
PC
Strieter
R M
RM
Gauldie
J
J
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000235:genetics*; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008168:Lung / Q000166:cytology* / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D051381:Rats; D017207:Rats, Sprague-Dawley
C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D017931:DNA Primers; D036341:Intercellular Signaling Peptides and Proteins; D015847:Interleukin-4; D007371:Interferon-gamma