Local pulmonary immune stimulation by the Toll-like receptor 2 and 6 ligand MALP-2 in rats is age dependent.
Recent studies indicate that the pulmonary immune response in humans and experimental animals is different in newborn, adult and elderly age groups. The aim of this study was to investigate the influence of age on the leukocyte composition in different lung compartments and peripheral blood of weaned and adult rats. A mycoplasma-like inflammatory response was mimicked by intratracheal application of the synthetic macrophage-activating lipopeptide-2 (MALP-2) which activates macrophages and other cells via the Toll-like receptor (TLR) 2 and 6. TLR 2 and 6 mRNA expressions were investigated by semiquantitative RT-PCR in cells of the bronchoalveolar lavage (BAL) and lung interstitium. Weaned Lewis rats (3-4 weeks old) and adults (12-14 months old) were treated with vehicle control or MALP-2. Cytokines and cell infiltration were measured in the BAL and lung interstitium. In control rats, no differences in TLR 2 and 6 mRNA expression level were found between the age groups. After MALP-2 treatment, the maximum of MCP-1 concentration in the BAL fluid was reached in weaned rats after 4h and in adults after 2h. The TNF-alpha maximum was measured after 2h in both age groups. Three days after MALP-2 the numbers of different leukocyte subsets were significantly increased in the BAL of both groups. In contrast, in the lung interstitium MALP-2 induced a leukocyte increase in adult rats but not in weaned rats. In conclusion, data on pulmonary immune responses from one age group and one lung compartment should not be generalized or extrapolated to other groups.
Lührmann
Anke
A
Functional and Applied Anatomy, Medical School of Hannover, Hannover, Germany. luehrmann.anke@gmx.de
Grote
Karsten
K
Stephan
Michael
M
Tschernig
Thomas
T
Pabst
Reinhard
R
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000943:Antigens, Differentiation / Q000032:analysis; D001402:B-Lymphocytes / Q000166:cytology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002452:Cell Count; D018932:Chemokine CCL2 / Q000032:analysis / Q000378:metabolism; D003713:Dendritic Cells / Q000737:chemistry / Q000166:cytology; D015870:Gene Expression / Q000187:drug effects; D007114:Immunization; D017493:Leukocyte Common Antigens / Q000032:analysis; D055666:Lipopeptides; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology; D016676:Macrophages, Alveolar / Q000166:cytology; D008297:Male; D009000:Monocytes / Q000166:cytology; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D051216:Toll-Like Receptor 6 / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism
D000943:Antigens, Differentiation; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D055666:Lipopeptides; C459465:OX-62 antigen, rat; D009842:Oligopeptides; C495343:Tlr2 protein, rat; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6; D014409:Tumor Necrosis Factor-alpha; C106335:macrophage stimulatory lipopeptide 2; D017493:Leukocyte Common Antigens