PMID- 11798467 OWN - NLM STAT- MEDLINE DCOM- 20020328 LR - 20081121 IS - 1079-9907 (Print) IS - 1079-9907 (Linking) VI - 21 IP - 12 DP - 2001 Dec TI - Dysregulated response to mycobacterial cord factor trehalose-6,6'-dimycolate in CD1D-/- mice. PG - 1089-96 AB - The biologic effects of the mycobacterial glycolipid trehalose-6,6'-dimycolate (TDM) include granuloma formation and macrophage activation and are dependent on physical conformation. In mice, the group II CD1 surface molecule CD1d has been implicated in glycolipid presentation. The importance of CD1d interactions in pathology has yet to be established. We hypothesized that mice lacking CD1d (CD1D(-/-)) would demonstrate dysregulated granulomatous response to TDM, compared with CD1D(+/-) heterozygous controls. Mice were intravenously injected with TDM-coated polystyrene-divinylbenzene beads and examined for histologic response and for changes in inflammatory cytokine and chemokine mRNA. Control CD1D heterozygous mice demonstrated a granulomatous response, which peaked at day 5. Increased mRNA for tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-1alpha (MIP-1alpha) correlated with development of granulomas, with very little change in interleukin-1beta (IL-1beta) and monocyte chemoattractant protein-1 (MCP-1). In contrast, the CD1D(-/-) mice revealed markedly different responses. Five days after administration, severe pulmonary hemorrhage was induced. The relative size of inflammation surrounding coated bead in the CD1D(-/-) mice was nearly double that induced in the CD1D(+/-) mice. CD1D(-/-) mice also demonstrated elevated mRNA for both inflammatory cytokines and chemokines by day 1 after administration, significantly earlier than responses seen in the heterozygous controls. FAU - Actor, J K AU - Actor JK AD - Department of Pathology, University of Texas Houston Medical School, Houston, TX 77030, USA. Jeffrey.K.Actor@uth.tmc.edu FAU - Olsen, M AU - Olsen M FAU - Hunter, R L Jr AU - Hunter RL Jr FAU - Geng, Y J AU - Geng YJ LA - eng GR - R01-HL55969-01/HL/NHLBI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Interferon Cytokine Res JT - Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research JID - 9507088 RN - 0 (Antigens, CD1) RN - 0 (Antigens, CD1d) RN - 0 (Chemokines) RN - 0 (Cord Factors) RN - 0 (Cytokines) RN - 0 (RNA, Messenger) SB - IM MH - Animals MH - Antigens, CD1/*genetics MH - Antigens, CD1d MH - Chemokines/biosynthesis/genetics MH - Cord Factors/*pharmacology MH - Cytokines/biosynthesis/genetics MH - Granuloma, Respiratory Tract/immunology/*microbiology/pathology MH - Hemorrhage/microbiology/pathology MH - Lung Diseases/immunology/*microbiology/pathology MH - Mice MH - Mice, Knockout MH - Mycobacterium/*pathogenicity MH - Pneumonia/immunology/microbiology MH - RNA, Messenger/biosynthesis EDAT- 2002/01/19 10:00 MHDA- 2002/03/29 10:01 CRDT- 2002/01/19 10:00 PHST- 2002/01/19 10:00 [pubmed] PHST- 2002/03/29 10:01 [medline] PHST- 2002/01/19 10:00 [entrez] AID - 10.1089/107999001317205222 [doi] PST - ppublish SO - J Interferon Cytokine Res. 2001 Dec;21(12):1089-96. doi: 10.1089/107999001317205222.