TNF-alpha-dependent ICAM-1- and VCAM-1-mediated inflammatory responses are delayed in neonatal mice infected with Pneumocystis carinii.
Neonatal mice have a delayed CD4-mediated inflammatory response to Pneumocystis carinii (PC) infection in the lungs that corresponds to a delayed TNF-alpha response and a delayed clearance of the organisms compared with adult mice. Since TNF-alpha is known to drive the up-regulation of adhesion molecules, we examined the expression and function of adhesion molecules in the lungs of neonatal mice. The expression of both ICAM-1 and VCAM-1 was significantly lower in the lungs of PC-infected neonatal mice compared with adults. Additionally, migration of neonatal T cells across endothelial cells expressing VCAM-1 and monocyte chemotactic protein-1 was aberrant compared with that in adult T cells, although alpha(4)beta(1) integrin-mediated adhesion of neonatal lymphocytes was comparable to that of adult lymphocytes. Treatment of neonatal mice with exogenous TNF-alpha resulted in increased expression of ICAM-1 and VCAM-1 as well as increased expression of chemokines, resulting in infiltration of CD4(+) cells into the lungs. Treatment with exogenous TNF-alpha resulted in a trend (although not statistically significant) toward a reduction of PC organisms from the lungs. These data indicate that neonatal lung endothelial cells do not up-regulate ICAM-1 and VCAM-1 in response to PC infection, probably due to depressed TNF-alpha production. Additionally, neonatal T cells are defective in the ability to migrate across endothelial cells.
Department of Microbiology, University of Kentucky, Veterans Administration Medical Center, Lexington, KY 40536, USA.
Mahboob H
MH
Qureshi
Joan
J
Cook-Mills
Dennis E
DE
Doherty
Beth A
BA
Garvy
D000281:Administration, Intranasal; D000375:Aging / Q000276:immunology; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000276:immunology* / Q000382:microbiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002448:Cell Adhesion / Q000276:immunology; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D042783:Endothelial Cells / Q000276:immunology / Q000473:pathology; D018836:Inflammation Mediators / Q000502:physiology*; D039441:Integrin alpha4 / Q000096:biosynthesis; D019012:Integrin beta1 / Q000096:biosynthesis; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000502:physiology*; D008168:Lung / Q000254:growth & development / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D045363:Pneumocystis carinii / Q000276:immunology*; D011020:Pneumonia, Pneumocystis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000096:biosynthesis / Q000502:physiology*; D015854:Up-Regulation / Q000276:immunology
D018836:Inflammation Mediators; D019012:Integrin beta1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D039441:Integrin alpha4