PMID- 8103296 OWN - NLM STAT- MEDLINE DCOM- 19930930 LR - 20181113 IS - 0002-9440 (Print) IS - 1525-2191 (Electronic) IS - 0002-9440 (Linking) VI - 143 IP - 3 DP - 1993 Sep TI - Analysis of monocyte chemoattractant protein 1-mediated lung injury using rat lung organ cultures. PG - 894-906 AB - Using a rat lung organ culture system, we analyzed the role of monocyte chemoattractant protein 1 (MCP 1) in leukocyte to lung adhesive interactions and monocyte-mediated lung injury. Quantitative leukocyte to lung adhesive interactions were examined using an adaptation of the Woodruff-Stamper frozen section binding assay. Pretreatment of organ cultures with recombinant human tumor necrosis factor (rhTNF alpha) resulted in a protein synthesis-dependent increase in the adhesiveness of lung tissue for peripheral blood monocytes. Adhesion of monocytes to lung tissue was not increased above baseline after 7 hours but increased more than twofold by 24 hours and persisted through 48 hours. Binding of monocyte to lung tissue was further increased when recombinant rat MCP 1 was added to monocyte suspensions immediately before being layered onto lung sections derived from either TNF alpha-treated or untreated organ cultures. Addition of antibody directed against rat CD11b/c resulted in a moderate reduction in monocyte binding. TNF or lipopolysaccharide-induced activation of mononuclear cells in the presence of [3H]leucine-labeled organ cultures resulted in lung injury as assessed by radioisotope release. Mononuclear cell-mediated organ culture injury could be partially inhibited with anti-rat MCP 1 antibody, anti-rat CD11b/c antibody, or antioxidants including catalase and deferoxamine. Anti-MCP 1 and anti-CD11b/c increased the absolute numbers of monocytes that could be retrieved from monocyte-lung co-cultures while catalase and deferoxamine did not. In vitro studies revealed that isolated rat peripheral blood monocytes produce O2- in response to MCP 1. These data provide a functional correlate for recent in vitro studies which suggest that MCP 1 may mediate leukocyte adhesive processes by up-regulating beta 2 integrin expression on monocytes. This study provides evidence that monocytes activated by MCP 1 can damage lung tissue through an oxidant-mediated mechanism. Monocyte chemoattractant protein 1 may participate in the pathogenesis of monocyte-mediated lung injury by modulating inflammatory cell adhesion as well as through monocyte activation. FAU - Warren, J S AU - Warren JS AD - Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602. FAU - Jones, M L AU - Jones ML FAU - Flory, C M AU - Flory CM LA - eng GR - HL07517/HL/NHLBI NIH HHS/United States GR - HL40526/HL/NHLBI NIH HHS/United States GR - HL48287/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Am J Pathol JT - The American journal of pathology JID - 0370502 RN - 0 (Antigens, CD) RN - 0 (CD11 Antigens) RN - 0 (Chemokine CCL2) RN - 0 (Chemotactic Factors) RN - 0 (Oxidants) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 1.11.1.6 (Catalase) RN - J06Y7MXW4D (Deferoxamine) SB - IM MH - Animals MH - Antigens, CD/metabolism MH - CD11 Antigens MH - Catalase/metabolism MH - Cell Adhesion/physiology MH - Chemokine CCL2 MH - Chemotactic Factors/*analysis/physiology MH - Deferoxamine/pharmacology MH - Kinetics MH - Lung/drug effects/*metabolism/pathology MH - Male MH - Monocytes/physiology MH - Organ Culture Techniques MH - Oxidants/metabolism MH - Rats MH - Tumor Necrosis Factor-alpha/pharmacology PMC - PMC1887221 EDAT- 1993/09/01 00:00 MHDA- 1993/09/01 00:01 PMCR- 1994/03/01 CRDT- 1993/09/01 00:00 PHST- 1993/09/01 00:00 [pubmed] PHST- 1993/09/01 00:01 [medline] PHST- 1993/09/01 00:00 [entrez] PHST- 1994/03/01 00:00 [pmc-release] PST - ppublish SO - Am J Pathol. 1993 Sep;143(3):894-906.