Expression and participation of eotaxin during mycobacterial (type 1) and schistosomal (type 2) antigen-elicited granuloma formation.
Eotaxin participation was analyzed during types 1 and 2 lung granuloma formation induced by embolizing Sepharose beads coupled to purified protein derivative (PPD) of Mycobacterium bovis or soluble Ags derived from Schistosoma mansoni eggs. Eotaxin was monitored by protein ELISA and semiquantitative reverse-transcriptase PCR mRNA analysis. Both types 1 and 2 granulomas released eotaxin, but levels were sixfold greater (on day 4) in the type 2 than for the type 1 or foreign body granulomas. Transcripts for eotaxin, IL-4, and CCR3 (eotaxin receptor) were also enhanced during type 2 granuloma formation. Anti-IL-4 treatment impaired eotaxin mRNA in lungs with type 2 granulomas, indicating that IL-4 promoted local eotaxin expression. In vivo, anti-eotaxin treatment caused modest reductions in the size of both types 1 and 2 lesions, with negligible effect on eosinophil recruitment. Surprisingly, anti-eotaxin treatment abrogated IFN-gamma-producing cells in regional lymph nodes during the type 1 PPD response. Lymph nodes draining both types 1 and 2 lesions showed enhanced CCR3 mRNA, but this followed the time of maximum eotaxin protein and mRNA expression. Correlative, in vitro studies revealed that graded doses of eotaxin increased IFN-gamma production from PPD-sensitive regional lymph node cultures, while monocyte-chemotactic protein-1, an important macrophage chemoattractant, had the opposite effect. These findings indicate that eotaxin expression is not limited to type 2 hypersensitivity granulomas, but also promotes IFN-gamma production during mycobacterial responses.
Department of Pathology and Laboratory Medicine, Veterans Affairs Medical Center, Ann Arbor, MI 48105, USA.
J H
JH
Ruth
N W
NW
Lukacs
K S
KS
Warmington
T J
TJ
Polak
M
M
Burdick
S L
SL
Kunkel
R M
RM
Strieter
S W
SW
Chensue
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D000947:Antigens, Helminth / Q000276:immunology*; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D005260:Female; D006099:Granuloma / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D009163:Mycobacterium bovis / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000276:immunology; D012550:Schistosoma mansoni / Q000276:immunology*
D000942:Antigens, Bacterial; D000947:Antigens, Helminth; C515457:Ccl11 protein, mouse; C515351:Ccr3 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D012333:RNA, Messenger; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D015847:Interleukin-4